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Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury 被引量:13
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作者 Qi-shan Ran Yun-hu Yu +1 位作者 Xiao-hong Fu Yuan-chao Wen 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第8期1258-1264,共7页
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injur... The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma. 展开更多
关键词 nerve regeneration endothelial progenitor cells traumatic brain injury notch signaling pathway cell migration INVASION ANGIOGENESIS jet PEI? system neural regeneration
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Astrocyte-neuron communication mediated by the Notch signaling pathway:focusing on glutamate transport and synaptic plasticity 被引量:6
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作者 Ke-Xin Li Meng Lu +2 位作者 Meng-Xu Cui Xiao-Ming Wang Yang Zheng 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第10期2285-2290,共6页
Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalitie... Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalities for reducing glutamate accumulation.However,further research is needed to investigate the dynamic changes in and molecular mechanisms of glutamate transport and the effects of glutamate transport on synapses.The aim of this study was to investigate the regulatory mechanisms underlying Notch pathway mediation of glutamate transport and synaptic plasticity.In this study,Yorkshire neonatal pigs(male,age 3 days,weight 1.0–1.5 kg,n=48)were randomly divided into control(sham surgery group)and five hypoxic ischemia subgroups,according to different recovery time,which were then further subdivided into subgroups treated with dimethyl sulfoxide or a Notch pathway inhibitor(N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester).Once the model was established,immunohistochemistry,immunofluorescence staining,and western blot analyses of Notch pathway-related proteins,synaptophysin,and glutamate transporter were performed.Moreover,synapse microstructure was observed by transmission electron microscopy.At the early stage(6–12 hours after hypoxic ischemia)of hypoxic ischemic injury,expression of glutamate transporter excitatory amino acid transporter-2 and synaptophysin was downregulated,the number of synaptic vesicles was reduced,and synaptic swelling was observed;at 12–24 hours after hypoxic ischemia,the Notch pathway was activated,excitatory amino acid transporter-2 and synaptophysin expression was increased,and the number of synaptic vesicles was slightly increased.Excitatory amino acid transporter-2 and synaptophysin expression decreased after treatment with the Notch pathway inhibitor.This suggests that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin. 展开更多
关键词 ASTROCYTE astrocyte-neuron communication glutamate glutamate transporter hypoxic-ischemic injury magnetic resonance spectroscopy NEONATE notch signaling pathway plasticity SYNAPSE
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Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension 被引量:6
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作者 Lei Li Li-Ping Chen Qing-Huai Liu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第2期208-215,共8页
AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells(RGCs) and optic nerve in rats with acute ocular hypertension(OH).METHODS: Totally 48 Sprague-Dawley(SD) rats were included, a... AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells(RGCs) and optic nerve in rats with acute ocular hypertension(OH).METHODS: Totally 48 Sprague-Dawley(SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution(PBS) and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor(DAPT). Quantitative real-time polymerase chain reaction(qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43(GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS: The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION: The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH. 展开更多
关键词 notch signaling pathway ocular hypertension retinal ganglion cells anti-apoptotic neuroprotection growth-associated protein
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Protective Effect of Catalpol on Myocardium in Rats with Isoprenaline-Induced Myocardial Infarcts via Angiogenesis through Endothelial Progenitor Cells and Notch1 Signaling Pathway 被引量:2
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作者 Jing Zeng Feng Huang +3 位作者 Yuangqing Tu Saichun Wu Manping Li Xiaoyun Tong 《Pharmacology & Pharmacy》 2013年第8期619-627,共9页
Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To anal... Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To analyze the pathological status and impact of catalpol on the rats, 3 weeks after intragastric gavage, the animals were verified for myocardial infarcts with electrocardiogram and measured for enzyme activity of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) and superoxide dismutase (SOD) in myocardium, and further analyzed using HE and TTC staining, as well as visual examination of infarct area. Flow cytometry study of endothelial progenitor cells (EPCs) indicated that the EPCs were mobilized during infarction. The roles of Notch1 signaling pathway in angiogenesis of the infracted animals were studied using immunohistochemistry analysis of RBPjκ and Western blot analysis of Notch1 and Jagged1. Our results obtained from the rats treated with catalpol, positive drug and control showed that catalpol could protect rats from infarction probably by mobilization of EPCs and activation of Notch1 signaling pathway. 展开更多
关键词 Myocardial Infarction Endothelial PROGENITOR Cell notch1 signaling pathway ANGIOGENESIS CATALPOL
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Acupuncture and moxibustion for the prevention of contrast induced nephropathy in diabetic rats by inhibiting Notch signaling pathway
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作者 Kai Zhao 《中国循环杂志》 CSCD 北大核心 2018年第S01期150-151,共2页
Objective Apoptosis is recognized as an important mechanism in contrast-induced nephropathy(CIN).Acupuncture and moxibustion,the auxiliary treatment in China,are effective interventions for cell apoptosis in many isch... Objective Apoptosis is recognized as an important mechanism in contrast-induced nephropathy(CIN).Acupuncture and moxibustion,the auxiliary treatment in China,are effective interventions for cell apoptosis in many ischemic diseases.In our previous study,we found acupuncture and moxibustion could prevent CIN.The objective of this research is to study the mechanism of acupuncture and moxibustion on tubular epithelial cell apoptosis in diabetic CIN rats. 展开更多
关键词 INHIBITING notch signaling pathway contrast-induced NEPHROPATHY ISCHEMIC diseases
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Role of the Notch Signaling Pathway in Fibrosis of Denervated Skeletal Muscle
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作者 Fei FENG Lu SHAN +2 位作者 Jing-xiu DENG Ling-li LUO Qi-shun HUANG 《Current Medical Science》 SCIE CAS 2019年第3期419-425,共7页
In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Gro... In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle. 展开更多
关键词 notch signaling pathway SCIATIC nerve skeletal muscle FIBROSIS N-[N-(3 5- difluorophenacetyl)-l-alanyl]-S-phenylglycine T-BUTYL ester notch 1 JAGGED 1 Hes 1 collagen I denervated muscular atrophy
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Effect of Tripterine on Notch Signaling Pathway in IgA Nephropathy Rats
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作者 Dan Liu 《Journal of Clinical and Nursing Research》 2018年第6期8-12,共5页
The objective of the study was to investigate the effect of tripterine on the Notch signaling pathway in renal tissue of IgA nephropathy rats.SD male rats were divided into the control group,IgA nephropathy model grou... The objective of the study was to investigate the effect of tripterine on the Notch signaling pathway in renal tissue of IgA nephropathy rats.SD male rats were divided into the control group,IgA nephropathy model group,benazepril group,1 mg/kg/day tripterine intervention group,and 10 mg/kg/day tripterine intervention group according to the random number table method,with 10 rats in each group.The urinary sediment and 24-h urinary protein quantity were detected by conventional methods.The expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats were detected by real-time fluorescent quantitative polymerase chain reaction.IgA nephropathy model was successfully established.The hematuria and proteinuria in model group were higher than those of control group(P<0.05).The expressions of Notch1,Jagged1,Hes1,and hey1 in kidney tissue of IgA nephropathy rats were significantly increased(P<0.05).Compared with the model group,hematuria and proteinuria in the tripterine intervention group were alleviated.The expressions of Notch1,Jagged1,Hes1,and Hey1 in rat renal tissue were decreased(P<0.05).Moreover,the expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats in 10 mg/kg/day tripterine intervention group were decreased(P<0.05).Tripterine can decrease the levels of hematuria and proteinuria in IgA nephropathy rats.The expression of the Notch signaling pathway in IgA nephropathy rats is increased by the down-regulation of tripterine,suggesting that tripterine has a certain therapeutic effect on IgA nephropathy rat.Moreover,its role may be realized through this signal pathway so as to provide a new mentality for the diagnosis and treatment of IgA nephropathy. 展开更多
关键词 IGA NEPHROPATHY notch signaling pathway tripterine RATS
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Research progress of Notch signaling pathway and biological behavior of tumor
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作者 Su Yan Peng Wang Yi-Dong Wang 《Journal of Hainan Medical University》 2019年第13期72-76,共5页
As an important signal transduction pathway between cells, Notch signaling pathway plays a very important role in cell recognition, proliferation, differentiation ,and apoptosis. At the same time, more and more relate... As an important signal transduction pathway between cells, Notch signaling pathway plays a very important role in cell recognition, proliferation, differentiation ,and apoptosis. At the same time, more and more related studies show that abnormal activation of Notch signaling pathway plays an important role in the occurrence and development of a variety of malignant tumors, and has become a hot topic in the field of tumor research. Instead of focusing on the relationship between Notch signaling pathway and various organ tumors or the relationship between Notch signaling pathway and tumor single regulatory factors, this paper focuses on the role of Notch signaling pathway by summing up and summarizing the role of the signal pathway. A series of biological behaviors of the tumor, such as angiogenesis, invasion, and metastasis, involved in Notch signaling pathway, are reviewed in this paper, as well as the recent advances in the regulation of tumor biological behavior, such as angiogenesis, invasion, metastasis and so on. 展开更多
关键词 TUMOR notch signaling pathway Mechanism TARGET Research PROGRESS
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Effect of spinal cord extracts after spinal cord injury on proliferation of rat embryonic neural stem cells and Notch signal pathway in vitro 被引量:9
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作者 Qing-Zhong Zhou Ge Zhang +6 位作者 Hai-Bo Long Fei Lei Fei Ye Xu-Feng Jia Yun-Long Zhou Jian-Ping Kang Da-Xiong Feng 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2014年第7期562-567,共6页
Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1... Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene. 展开更多
关键词 Neural stem CELL CELL culture Spinal CORD extract notch signal pathway
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Notch signalling pathway in development of cholangiocarcinoma 被引量:4
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作者 Bisma Rauff Arif Malik +3 位作者 Yasir Ali Bhatti Shafiq Ahmad Chudhary Ishtiaq Qadri Shafquat Rafiq 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2020年第9期957-974,共18页
Cholangiocarcinoma(CCA)comprises of extra-hepatic cholangiocarcinoma and intrahepatic cholangiocarcinoma cancers as a result of inflammation of epithelium cell lining of the bile duct.The incidence rate is increasing ... Cholangiocarcinoma(CCA)comprises of extra-hepatic cholangiocarcinoma and intrahepatic cholangiocarcinoma cancers as a result of inflammation of epithelium cell lining of the bile duct.The incidence rate is increasing dramatically worldwide with highest rates in Eastern and South Asian regions.Major risk factors involve chronic damage and inflammation of bile duct epithelium from primary sclerosing cholangitis,chronic hepatitis virus infection,gallstones and liver fluke infection.Various genetic variants have also been identified and as CCA develops on the background of biliary inflammation,diverse range of molecular mechanisms are involved in its progression.Among these,the Notch signalling pathway acts as a major driver of cholangiocarcinogenesis and its components(receptors,ligands and downstream signalling molecules)represent a promising therapeutic targets.Gamma-Secretase Inhibitors have been recognized in inhibiting the Notch pathway efficiently.A comprehensive knowledge of the molecular pathways activated by the Notch signalling cascade as well as its functional crosstalk with other signalling pathways provide better approach in developing innovative therapies against CCA. 展开更多
关键词 Cholangicarcinoma notch receptors Therapeutic targets notch signalling pathway Gamma secretase inhibitor CHOLANGIOCYTES
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Effects of the Nocth signaling pathway on expression of inflammatory factors and transforming growth factors in diabetic foot ulcers 被引量:1
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作者 Qiang Han Guo-Bin Liu +4 位作者 Ren-Yan Huang Feng Xu Shi-Meng Yan Chen-Yan Shi Jun-Hao Chen 《Journal of Hainan Medical University》 2021年第12期1-1,共1页
Objective:persistent hyperinflammation is an important reason for the development of diabetic foot ulcer.Notch signaling is an important signaling pathway involved in the inflammatory response and cell proliferation i... Objective:persistent hyperinflammation is an important reason for the development of diabetic foot ulcer.Notch signaling is an important signaling pathway involved in the inflammatory response and cell proliferation in diabetic foot ulcer rats.This paper aims to explore the effect of Notch signaling on inflammatory factors,chemokines and growth factors through the intervention of Notch signaling in diabetic foot ulcer rats.Methods:the experimental model was made by using high-fat feed combined with streptozotocin(STZ)to cause diabetes,and the experimental model of diabetic foot ulcer was established by constant temperature and constant pressure scald apparatus.The normal ulcer model was used as a control.The intervention controls of the experimental model included normal saline,western medicine growth factor,Notch agonist Jagged1,Notch signaling inhibitor ly-411575,and the intervention of traditional Chinese medicine Zizhu ointment for 7 days.Serum il-1,il-6,TNF-radiation,and il-17 were detected by ELISA.Real-time PCR was used to detect the inflammatory factors,chemokines,and growth factors associated with Notch signaling in wound tissues:tnf-uum,il-1,il-6,il-17,interleukin-8,ip-10,McP-1,TGF-uum,TGF-livelihood.Results:serum levels of il-1,il-6,TNF-radiation and il-17 in diabetic foot ulcer rats were significantly higher than that in normal ulcer rats.The contents of il-1,il-6,TNF-radiation and il-17a in ly-411575 group and Zizhu ointment group were significantly reduced.Real-time PCR results of wound tissue showed that the levels of inflammatory cytokines il-1,il-6,TNF-radiation,il-17 and chemokines ip-10,il-8 and McP-1 in the wound tissue of diabetic foot ulcer rat model were significantly higher than that of normal ulcer model,and the levels of growth factor TGF-exposure were lower than that of normal ulcer model.LY-411575 significantly reduced il-1,il-6,TNF-maxima,il-17,and the chemokines ip-10,il-8,and McP-1 in diabetic foot ulcer rats,and reduced the expression of TGF-,TGF-earth.Jagged1 can increase the expression of TGF--,TGF---,suggesting that inhibition of the Notch signaling pathway can reduce the expression of the inflammatory factors il-1,il-6,TNF--,il-17a,il-8,and the growth factors TGF--,TGF---.Zizhu ointment can reduce the levels of il-1,il-6,TNF-benand,il-17,and the chemokines ip-10,il-8,and McP-1 on the wound surface of diabetic foot rats,and improve the expression of TGF-benand TGF-SUNS.Ly-411575 inhibited the expression of TGF-bento and TGF-promoting of Zizhu ointment.Conclusion:the expression of inflammatory cytokines and chemokines was higher and the expression of growth factors was lower in diabetic foot ulcer rats than in normal ulcer rats.Inhibition of Notch signaling pathway can reduce the expression of inflammatory factors,chemokines and growth factors in experimental model rats,and Notch signaling pathway can promote inflammation and cell proliferation.Zizhu ointment can reduce the levels of inflammatory cytokines and chemokines in diabetic foot ulcer rats,improve the expression of growth factors,and reduce wound inflammation,which may be related to the inhibition of Nocth signal expression. 展开更多
关键词 notch signaling pathway Diabetic foot ulcer Inflammatory factor Transforming growth factor
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Notch_2-Delta在体外人牙髓细胞分化中的表达及调控 被引量:3
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作者 何飞 谭颖徽 杨峥嵘 《华西口腔医学杂志》 CAS CSCD 北大核心 2003年第5期344-346,371,共4页
目的 探讨Notch信号在体外牙髓细胞向成牙本质样细胞分化过程中的作用。方法 人牙髓细胞体外连续培养 ,采用免疫组化染色及Westernblot方法对该过程中人牙髓细胞Notch2 _Delta的表达及rhBMP_2对Delta表达的影响进行定性及半定量研究... 目的 探讨Notch信号在体外牙髓细胞向成牙本质样细胞分化过程中的作用。方法 人牙髓细胞体外连续培养 ,采用免疫组化染色及Westernblot方法对该过程中人牙髓细胞Notch2 _Delta的表达及rhBMP_2对Delta表达的影响进行定性及半定量研究。结果 体外牙髓细胞增殖、分化过程中有Notch2 _Delta的表达 ,随细胞增殖、分化状态的不同 ,二者表达的部位及表达强度发生变化 ,外源性rhBMP_2在牙髓细胞结节形成后期可上调Delta的表达。结论 Notch信号途径参与了体外牙髓细胞向成牙本质样细胞分化过程 ,其介导的细胞间相互作用可能是控制牙髓细胞对信号分子反应性的机制。 展开更多
关键词 notch2 delta 人牙髓细胞 细胞分化 细胞培养 信号转导
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Notch配体Delta-like-1和Jagged-1 mRNA在骨髓增生异常综合征患者骨髓间充质干细胞中表达研究 被引量:3
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作者 费成明 顾树程 +3 位作者 赵佑山 郭娟 李晓 常春康 《中国实验血液学杂志》 CAS CSCD 北大核心 2014年第6期1656-1660,共5页
本研究检测骨髓增生异常综合征(MDS)患者骨髓间充质干细胞Notch信号通路配体Delta-like-1和Jagged-1 mRNA表达水平,探讨其与M DS发病的关系。采用实时荧光定量聚合酶链反应检测38例M DS患者和16例正常对照者骨髓间充质干细胞中Delta-lik... 本研究检测骨髓增生异常综合征(MDS)患者骨髓间充质干细胞Notch信号通路配体Delta-like-1和Jagged-1 mRNA表达水平,探讨其与M DS发病的关系。采用实时荧光定量聚合酶链反应检测38例M DS患者和16例正常对照者骨髓间充质干细胞中Delta-like-1和Jagged-1的基因表达水平。结果表明,MDS患者的Delta-like-1和Jagged-1 mRNA表达水平较正常对照组均明显升高(P<0.05)。在WHO分组中,RA/RARS、RCMD及RAEB组Delta-like-1的表达量均高于正常对照组(P<0.05),RARB组Jagged-1与正常对照组差异有显著性(P<0.05)。Delta-like-1表达与骨髓原始细胞比例有显著相关性(r=0.502,P<0.05)。伴染色体异常M DS组Deltalike-1和Jagged-1 mRNA表达水平较无染色体异常M DS组明显升高(P<0.05)。在IPSS分组中,较高危组Deltalike-1表达显著高于较低危组(P<0.01),而Jagged-1表达在两组间无统计学差异(P>0.05)。结论:M SC中Delta-like-1和Jagged-1高表达可能参与了M DS的发病过程。 展开更多
关键词 骨髓增生异常综合征 骨髓间充质干细胞 notch信号通路 delta-like-1 JAGGED-1
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首乌益智胶囊对血管性痴呆大鼠Notch/Delta信号通路TACE、PS1mRNA表达的影响 被引量:5
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作者 杨晓妮 李长生 +1 位作者 王运满 张志友 《上海中医药杂志》 2010年第4期58-61,共4页
目的观察中药首乌益智胶囊对血管性痴呆大鼠Notch/Delta信号通路TACE、PS1mRNA的影响,探讨其可能的作用机制。方法用改良Pulsinelli四血管阻断法制备血管性痴呆大鼠模型,随机分为首乌益智胶囊组、脑复康组、模型组,每组14只,并设假手术... 目的观察中药首乌益智胶囊对血管性痴呆大鼠Notch/Delta信号通路TACE、PS1mRNA的影响,探讨其可能的作用机制。方法用改良Pulsinelli四血管阻断法制备血管性痴呆大鼠模型,随机分为首乌益智胶囊组、脑复康组、模型组,每组14只,并设假手术组14只。分别给予相应的药物,20天后利用实时荧光定量PCR检测Notch/Delta信号通路TACE、PS1mRNA的表达。结果首乌益智胶囊组、脑复康组、模型组与假手术组比较,TACE、PS1基因相对定量表达差异有统计学意义(P<0.01);首乌益智胶囊组较脑复康组和模型组TACE、PS1基因表达明显增高(P<0.05,P<0.01)。结论首乌益智胶囊的有效成分可能通过激活Notch/Delta信号通路发挥作用,促进神经干细胞向星形胶质细胞分化,从而使得星形胶质细胞增殖,合成和分泌更多的神经营养因子、生长因子和其他活性物质。 展开更多
关键词 血管性痴呆 首乌益智胶囊 notch/delta信号通路 TACE MRNA PS1 MRNA
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斑马鱼Notch信号通路配体基因delta-like4对smad基因的调控作用
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作者 程瑶 王子睿 +4 位作者 周泽斌 张鹏 邱军强 李伟明 张庆华 《大连海洋大学学报》 CAS CSCD 北大核心 2023年第1期76-85,共10页
为研究斑马鱼(Danio rerio)的Notch信号通路配体delta-like 4(dll4)对smad基因(smad1和smad7)的调控作用,利用qRT-PCR方法检测受精后2 d(day post fertilization,dpf)的斑马鱼dll4纯合突变体smad家族中smad1和smad7的表达变化,利用生物... 为研究斑马鱼(Danio rerio)的Notch信号通路配体delta-like 4(dll4)对smad基因(smad1和smad7)的调控作用,利用qRT-PCR方法检测受精后2 d(day post fertilization,dpf)的斑马鱼dll4纯合突变体smad家族中smad1和smad7的表达变化,利用生物信息学软件预测smad1和smad7启动子序列的转录结合位点和CpG岛;采用同源重组的方法,构建p3×Flag-CMV-dll4真核表达载体及pGL3-smad1-Luc和pGL3-smad7-Luc报告基因载体,并通过双荧光素酶试验检测dll4对smad1和smad7的调控活性;分别转染两种启动子报告基因载体到HEK293T细胞,共转染启动子报告基因载体与真核表达载体到HEK293T细胞。结果表明:dll4纯合突变体斑马鱼中smad1和smad7表达量均显著下调(P<0.0001);两种基因启动子均包含HNF-3、GATA-1和Oct-1等转录因子结合位点,只有smad7启动子存在CpG岛;报告基因pGL3-smad1-Luc和pGL3-smad7-Luc的活性分别为对照组的7.3倍和142.7倍,两种报告基因与p3×Flag-CMV-dll4表达载体共转后,转录活性均升高,分别为对照组的2.8倍和2.2倍,说明p3×Flag-CMV-dll4可以促进pGL3-smad1-Luc和pGL3-smad7-Luc的转录表达活性。研究表明,斑马鱼Notch信号通路配体基因dll4可通过smad基因家族在血管生成中发挥调控作用,为损伤血管的修复和肿瘤血管生成提供特异的生物学靶点。 展开更多
关键词 斑马鱼 notch信号通路配体 delta-like 4 SMAD1 SMAD7 双荧光素酶报告基因
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Notch信号通路——对健康和疾病的机械论观点 被引量:1
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作者 Yao Meng Zhihan Bo +2 位作者 Xinyi Feng Xinyi Yang Penny A.Handford 《Engineering》 SCIE EI CAS CSCD 2024年第3期212-232,共21页
The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Se... The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases. 展开更多
关键词 notch signaling pathway Structural biology GLYCOSYLATION Genetic disorders CANCER Pharmacological agents
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Changes and correlation of inflammatory polarization and Notch pathway in rats with adjuvant arthritis
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作者 Lei Zhao Lei Wan +9 位作者 Jian Liu Chuan-Bing Huang Guang-Han Sun Xi-Meng Ma Zi-Heng Zhu Shu Li Fang-Ze Li Tian-Yang Liu Lei Liu Ming Li 《Journal of Hainan Medical University》 2021年第22期1-5,共5页
Objective:To investigate the relationship between inflammatory polarization and Notch pathway in rats with adjuvant arthritis.Methods:Twelve rats were randomly divided into normal(NC)group(n=6)and model(MC)group(n=6).... Objective:To investigate the relationship between inflammatory polarization and Notch pathway in rats with adjuvant arthritis.Methods:Twelve rats were randomly divided into normal(NC)group(n=6)and model(MC)group(n=6).In the model group,complete Freund's adjuvant(0.1ml/rat)was injected into the right hindfoot to induce inflammation.On the 12th day after inflammation,the changes of plantar swelling degree(E)and arthritis index(AI)were observed,and the expressions of inflammatory polarization markers CD68 and CD206 in peripheral blood were detected by flow cytometry.PCR was used to detect the expression of factors related to Notch signal pathway in peripheral blood.Results:Compared with the normal group,the expression of E,AI,CD68,Notch2,Notch3,Notch4 and Delta1 in the model group increased significantly,while the expression of CD206,Notch1,Jagged1 and Jagged2 decreased(P<0.01or P<0.05).The results showed that CD68,toe swelling degree and arthritis index were negatively correlated with Notch1,Jagged1 and Jagged2,CD68,toe swelling degree and arthritis index were positively correlated with Notch2,Notch4 and Delta1,CD206 was positively correlated with Notch1 and Jagged1,Jagged2 and CD206 was negatively correlated with Notch2,Notch4 and Delta1.Conclusion:Notch signal pathway may promote the occurrence and development of AA by regulating inflammatory polarization of macrophages. 展开更多
关键词 Adjuvant arthritis Inflammatory polarization notch signaling pathway MACROPHAGES
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Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling
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作者 Jingteng Chen Ling Yu +11 位作者 Tian Gao Xiangyang Dong Shiyu Li Yinchu Liu Jian Yang Kezhou Xia Yaru Yu Yingshuo Li Sen Wang ZhengFu Fan Hongbing Deng Weichun Guo 《Bioactive Materials》 SCIE CSCD 2024年第7期459-476,共18页
Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit os... Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit osteogenic cell ingrowth and vascularization,which is critical for bone regeneration.In the current study,we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix(ECM)-mimicking electrospun silk fibroin(SF)nanofibers.The SF-embedded MPC(SM)exhibited a heterogeneous and hierarchical structure,which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth.Besides,the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide.Bone marrow stem cells(BMSCs)adhered excellently on SM,as illustrated by formation of more pseudopodia.CCK8 assay showed that SM promoted early proliferation of BMSCs.Our study also verified that SM increased the expression of OPN,RUNX2 and BMP2,suggesting enhanced osteogenic differentiation of BMSCs.We screened for osteogenesis-related pathways,including FAK signaing,Wnt signaling and Notch signaling,and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway,proved by the downregulation of NICD1,Hes1 and Hey2.In addition,using a bone defect model of rat calvaria,the study revealed that SM exhibited enhanced osteogenesis,bone ingrowth and vascularization compared with MPC alone.No adverse effect was found after implantation of SM in vivo.Overall,our novel SM exhibited promising prospects for the treatment of critical-sized bone defects. 展开更多
关键词 Critical-sized bone defects Magnesium phosphate bone cement Silk fibroin nanofibers Bone regeneration notch signaling pathway
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Notch信号通路与Neuralized蛋白 被引量:1
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作者 郭政 黄瑾 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2008年第11期987-991,共5页
Notch信号通路在脊椎动物和无脊椎动物许多组织的发育过程和细胞间通讯中都发挥了关键的作用,包括调控细胞命运,调节细胞迁移,分化和增殖.Notch信号通路由Notch受体及其跨膜配体如Delta(Dl)和Serrate组成.Neuralized蛋白(Neur)编码1个E... Notch信号通路在脊椎动物和无脊椎动物许多组织的发育过程和细胞间通讯中都发挥了关键的作用,包括调控细胞命运,调节细胞迁移,分化和增殖.Notch信号通路由Notch受体及其跨膜配体如Delta(Dl)和Serrate组成.Neuralized蛋白(Neur)编码1个E3泛素连接酶,是Notch配体D1内吞所必需的.Neur蛋白包括3个从线虫到人高度保守的结构域:2个Neur同源重复结构域(NHR1和NHR2)和1个C端RING结构域.本文就Notch信号通路主要元件和Neru的结构与功能及其关系进行综述. 展开更多
关键词 notch信号通路 Neuralized蛋白 delta
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Notch1 downregulation combined with interleukin-24 inhibits invasion and migration of hepatocellular carcinoma cells 被引量:9
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作者 Bing Han Shi-Hai Liu +4 位作者 Wei-Dong Guo Bin Zhang Jian-Ping Wang Yu-Kun Cao Jun Liu 《World Journal of Gastroenterology》 SCIE CAS 2015年第33期9727-9735,共9页
AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to dow... AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to down-regulate Notch1.Hep G2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h.Cell viability was measured by MTT assay.The cellular and nuclear morphology was observed under a fluorescence microscope.To further verify the apoptotic phenotype,cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining.The expression of Notch1,SNAIL1,SNAIL2,E-cadherin,IL-24,XIAP and VEGF was detected by Western blot.The invasion and migration capacities of HCC cells were detected by wound healing assays.Notch1 and Snail were downregulated by RNA interference,and the target proteins were analyzed by Western blot.To investigate the mechanism of apoptosis,we analyzed Hep G2 cells treated with si Notch1 or si CON plus IL-24 or not for 48h by caspase-3/7 activity luminescent assay.RESULTS: GSI-I at a dose of 2.5 μmol/L for 24 h caused a reduction in cell viability of about 38% in Hep G2 cells.The addition of 50 ng/m L IL-24 in combination with 1 or 2.5 μmol/L GSI-I reduced cell viability of about 30% and 15%,respectively.Treatment with IL-24 alone did not induce any cytotoxic effect.In SMMC7721 cells with the addition of IL-24 to GSI-I(2.5 μmol/L),the reduction of cell viability was only about 25%.Following GSI-I/IL-24 combined treatment for 6 h,the apoptotic rate of Hep G2 cells was 47.2%,while no significant effect was observed in cells treated with the compounds employed separately.Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in Hep G2 cells.Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I.Furthermore,the increased GSI-I and IL-24 in Hep G2 cell was associated with downregulation of MMP-2,XIAP and VEGF.In the absence of treatment,Hep G2 cells could migrate into the scratched space in 24 h.With IL-24 or GSI-I treatment,the wound was still open after 24 h.And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I.Treatment of Notch-1 silenced Hep G2 cells with 50 ng/m L IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination.Caspase-3/7 activity was increased in the presence of si Notch1 plus IL-24 treatment.CONCLUSION: Down-regulation of Notch1 by GSI-I or si RNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of Hep G2 cells. 展开更多
关键词 notch signaling pathway INTERLEUKIN-24 Γ-SECRETASE
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