Protein tyrosine phosphatase 1B regulates migration of ARPE-19 cells through EGFR/ERK signaling pathway

AIMTo evaluate whether protein tyrosine phosphatase 1B (PTP1B) contributed to initiate human retinal pigment epithelium cells (A)-19 migration and investigate the signaling pathways involved in this process.METHODSARPE-19 cells were cultured and treated with the siRNA-PTP1B. Expression of PTP1B was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). AG1478 [a selective inhibitor of epidermal growth factor receptor (EGFR)] and PD98059 (a specific inhibitor of the activation of mitogen-activated protein kinase) were used to help to determine the PTP1B signaling mechanism. Western blot analysis verified expression of EGFR and extracellular signal-regulated kinase (ERK) in ARPE-19 cells. The effect of siRNA-PTP1B on cell differentiation was confirmed by immunostaining for α-smooth muscle actin (α-SMA) and qRT-PCR. Cell migration ability was analyzed by transwell chamber assay.RESULTSThe mRNA levels of PTP1B were reduced by siRNA-PTP1B as determined by qRT-PCR assay. SiRNA-PTP1B activated EGFR and ERK phosphorylation. α-SMA staining and qRT-PCR assay demonstrated that siRNA-PTP1B induced retinal pigment epithelium (RPE) cells to differentiate toward better contractility and motility. Transwell chamber assay proved that PTP1B inhibition improved migration activity of RPE cells. Treatment with AG1478 and PD98059 abolished siRNA-PTP1B-induced activation of EGFR and ERK, α-SMA expression and cell migration.CONCLUSIONPTP1B inhibition promoted myofibroblast differentiation and migration of ARPE-19 cells, and EGFR/ERK signaling pathway played important role in migration process.

Structural Insight into the Design on Oleanolic Acid Derivatives as Potent Protein Tyrosine Phosphatase 1B Inhibitors

Oleanolic acid derivatives act as newer protein tyrosine phosphatase 1B （PTP-1B） inhibitors for type 2 diabetes mellitus （T2DM）. In order to understand the structural requirement of PTP-1B inhibitors, 52 oleanolic acid derivatives were divided into a training set （34 compounds） and a test set （18 compounds）. The highly reliable and predictive 3D-QSAR models were constructed by CoMFA, CoMSIA and topomer CoMFA methods, respectively. The results showed that the cross validated coefficient （q2） and non-cross-validated coefficient （R2） were 0.554 and 0.999 in the CoMFA model, 0.675 and 0.971 in the CoMSIA model, and 0.628 and 0.939 in the topomer CoMFA model, which suggests that three models are robust and have good exterior predictive capabilities. Furthermore, ten novel inhibitors with much higher inhibitory potency were designed. Our design strategy was that （i） the electronegative substituents （Cl, -CH2OH, OH and -CH2Cl） were introduced into the double bond of ring C, （ii） the hydrogen bond acceptor groups （C≡N and N atom）, electronegative groups （C≡N, N atom, -COOH and -COOCH3） and bulky substituents （C6H5N） were connected to the C-3 position, which would result in generating potent and selective PTP-1B inhibitors. We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent PTP-1B inhibitors.

Synthesis and protein tyrosine phosphatase 1B inhibition activities of two new synthetic bromophenols and their methoxy derivatives

3-bromo-4,5-bis（2,3-dibromo-4,5-dihydroxybenzyl）-l,2-benzenediol （1） is a natural bromophenol isolated from the red algae Rhodomela confervoides that exhibits significant inhibition against protein tyrosine phosphatase 1B （PTP1B）. Based on its activity, we synthesized two new synthetic bromophenols and their methoxy derivatives from vanillin using the structure of natural bromophenol 1 as a scaffold. The structures of these bromophenols were elucidated from H NMR, 13C NMR, and high resolution electron ionization mass spectrometry as 2,3-dibromo-1-（2＇-bromo-6＇-（3＂,4＂-dimethoxybenzyl）- 3 ＇,4 ＇-dimethoxybenzyl）-4,5 -dimethoxybenzene （2）, 2,3-dibromo- 1 -（2 ＇-bromo-6＇-（2 ＂-bromo-4＂,5 ＂-dimethoxy- benzyl）-3＇,4＇-dimethoxybenzyl）-4,5-dimethoxybenzene （3）, 3,4-dibromo-5-（2＇-bromo-6＇-（2＂-bromo-4＂,5＂- dihydroxybenzyl）-3＇,4＇-dihydroxybenzyl）pyrocatechol （4） and 3,4-dibromo-5-（2＇-bromo-6＇-（3＂,4＂- dihydroxybenzyl）-3＇,4＇-dihydroxybenzyl）pyrocatechol （5）. PTP1B inhibition activities of these compounds were evaluated using a colorimetric assay, and compounds 3 and 4 demonstrated interesting activity against PTP1B.

A novel protein tyrosine phosphatase 1B inhibitor with therapeutic potential for insulin resistance

Insulin sensitizing medicines are currently limited, and identification of new drug candidate is a chal- lenge. Protein tyrosine phosphatase 1B （PTP1 B） negatively regulates insulin signaling pathway, and its inhibition is anticipated to improve insulin resistance. This study investigated the pharmacological profiles of compound CX08005, a new PTP1B inhibitor, with therapeutic potential for insulin resistance in vivo and in vitro, respective- ly. Recombinant human PTP1B protein was used to measure the enzyme activity. The docking simulation was per- formed to explore the interactions between the compound and the protein. The insulin sensitivity was evaluated in Diet-induced obesity mice and/or T2DM KKAy mice by glucose tolerance test （GTT）, the blood glucose level, glucose stimulated insulin secretion （GSIS）, homeostasis model assessment of insulin resistance index （HOMA-IR） and the whole-body insulin sensitivity （ISwb） index, respectively. The hyperinsulinemic-euglycemic clamp was performed to evaluate the insulin stimulated glucose disposal both in whole body and in insulin-sensitive tissues （muscle and fat）. Furthermore, its direct effect in muscle, fat and liver cells was observed. We found that CX08005 was a competitive inhibitor of PTP1B with dose-dependent activity （IC50=5.95 × 10^-7 M）. Docking simulation demonstrated that CX08005 binds to PTP1B at the catalytic P-loop through hydrogen bonds. In DIO mice, treatment with CX08005 effectively ameliorated glucose intolerance in a dose-dependent manner （50- 200 mg. kg^-1 · d^-l）, and decreased HOMA-IR values. We also demonstrated that oral administration of 50 mg ~ kg^-1· d^-1 CX08005 improved hyperglycemia, hyperinsulinemia, HOMA-IR and ISwb in KKAy mice. In hyperin- sulinemic-euglycemic clamp test, CX08005 increased glucose infusion rate and glucose uptake in muscle and fat of DIO mice. In 3T3-L1 adipocytes and C2C12 myotubes, CX08005 enhanced insulin-induced glucose uptake. In HepG2 hepatocyte, CX08005 enhanced insulin-stimulated tyrosine phosphorylation of IRβ/IRS1 in a dose-depend- ent manner, respectively; furthermore, the phosphorylation of several downstream molecules, including Akt, Foxol and GSK3β was also increased, indicating this compound could augment insulin＇s ability to suppress hepatic glu- cose output （HGO）. Our results strongly suggest that compound CX08005 directly enhances insulin action in vitro and in vivo with therapeutic potential for insulin resistance.

POM analysis and computational interactions of 8-hydroxydiospyrin inside active site of protein tyrosine phosphatase 1B

Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8-HDN)from D.lotus against the PTP1B enzyme.It showed significant inhibitory activity of PTP1B with an IC 50 value of 18.37±0.02μM.A detailed molecular docking study was carried out to analyze the binding orientation,binding energy,and mechanism of inhibition.A comparative investigation of 8-HDN in the catalytic,as well as the allosteric site of PTP1B,was performed.Binding energy data showed that compound 8-HDN is more selective for the allosteric site and hence avoids the problems associated with catalytic site inhibition.The inhibition mechanism of 8-HDN can be further investigated as an active lead compound against PTP1B by using in vitro and in vivo models.

Inactivation of Protein Tyrosine Phosphatase 1B （PTP1B） Activity by the Aqueous Partition of Guava Leaf Extract

Guava leaf tea has been used as a folk medicine for treating hyperglycemic conditions in Asia and Africa. The hypoglycemic efficacy of guava leaf has been documented by many scientists in these regions, but the hypoglycemic mechanism is poorly understood. Guava leaves were extracted with methanol and the crude extract was partitioned against hexane, ethyl acetate, and butanol in sequence. The leftover in water is defined as the aqueous partition. A second smaller batch was extracted with hot water directly. Oral glucose tolerance test was carried out on healthy mice instead of diabetic mice that lack endogenous insulin. Glucose uptake was examined with 3T3-L1 adipocytes. Oxidative effect on PTP1B （protein tyrosine phosphatase 1b） was carried out with real-time PTP1B enzymatic assay. The aqueous partition of guava leaf extract possesses a potent inhibitory effect on PTP1B enzymatic activity and this PTP1B inhibition is through a slow oxidative but reversible inactivation on the enzyme. The reversible inactivation would suggest guava leaf extract may augment PTP1B inhibition alongside the endogenous H2O2 which itself is induced by insulin. In addition, our study confirmed the hypoglycemic efficacy being associated with guava leaf and found the most effective molecules reside in the aqueous partition which is also less cytotoxic to Chinese hamster ovary cells when compared to other less polar partitions. The guava leaf extract can modulate insulin activity through a redox regulation on PP1B enzymatic activity. It is speculated that a compound similar to gallocatechin in the aqueous partition can reduce an oxygen molecule to hydrogen peroxide which in turn oxidizes the catalytic residue Cys in PTP1B. Therefore, the guava leaf tea can serve as a functional hypoglycemic drink that is suitable for either healthy or diabetic subjects.

Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B

Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

Bioactive chemical constituents from the marine-derived fungus Cladosporium sp.DLT-5

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

海藻中溴酚化合物的蛋白酪氨酸磷脂酶1B抑制活性研究

目的:通过对海藻天然产物进行活性筛选,寻找蛋白酪氨酸磷脂酶1B(PTP1B)抑制剂,为2型糖尿病和肥胖症的治疗寻找新的治疗药物。方法:以PTP1B为靶点,采用分子克隆谷胱苷肽巯基转移酶(glutathion Stransferase,GST)融合蛋白的方法,重组表达获得PTP1B,通过高通量筛选模型对海藻中得到的单体化合物进行活性筛选,采用LOGIT法计算LD50。结果:来源于松节藻和小黏膜藻的溴酚类化合物4-二溴-5-(甲氧基甲基)-1,2-二苯酚(1),2-甲基-3-(2,3-二溴-4,5-二羟基)-苯丙醛(2),3-(2,3-二溴-4,5-二羟基苯)-4-溴-5,6-二羟基-1,3-二氢异苯并呋喃(3)表现出显著的PTP1B抑制活性,IC50分别为3.4,4.5,2.8μmol.L-1。结论:首次对溴酚化合物作为PTP1B抑制剂进行研究,海藻中的3个溴酚类化合物表现出显著的PTP1B抑制活性,有开发成新型抗糖尿病海洋药物的潜力。

阿勒泰黄芪提取物对蛋白酪氨酸磷酸酯酶1B的抑制作用

本文探讨了阿勒泰黄芪不同提取物对蛋白酪氨酸磷酸酯酶1B(PTP1B)的抑制作用。采用分光光度法测定了提取物中的黄酮和皂苷含量;通过体外酶促动力学方法检测了不同提取物对PTP1B的影响,并确定了抑制类型;并采用氧化酶法检测了阿勒泰黄芪提取物对细胞利用葡萄糖能力的作用。结果表明,阿勒泰黄芪8种提取物(E1～8)中黄酮含量分别为5.09、10.46、3.58、3.23、53.91、21.77、5.76和7.49 mg/mL,其中E1、E2、E6、E7、E8皂苷含量分别为16.53、27.45、21.90、10.21和8.96 mg/mL;各提取物对PTP1B活性均表现出抑制作用,其中E1、E2、E7、E8的IC50分别为34.8、4.7、7.35和7.15μg/mL,E1、E7和E8是竞争性抑制,E2是混合型竞争性抑制。E1、E2、E5、E7和E8较明显的提高了CHO-K1细胞对葡萄糖的利用。提示皂苷可能是阿勒泰黄芪抑制PTP1B活性的主要物质,通过PTP1B途径有效了提高细胞利用葡萄糖的能力。本研究为阿勒泰黄芪开发为防治糖尿病及改善胰岛素抵抗的药物或保健品提供实验依据。

PTK和NF-κB参与HO-1对缺血-复灌心肌的保护作用

目的探讨酪氨酸激酶(PTK)和核转录因子(NF-κB)是否参与血红素氧化酶-1(HO-1)的诱导减轻心肌缺血和复灌损伤。方法SD大鼠40只随机分为A、B、C、D、E5组,每组8只,分别于腹腔注入生理盐水、HO-1诱导剂高铁血红素50mg/kg和HO-1抑制剂锌原卟啉IX(ZnPP)25μg/kg,或腹腔注入高铁血红素50mg/kg,并在24h后平衡灌流的后10min给予PTK抑制剂4,5,7-三羟基异丙酮10μmol/L及给予NF-κB抑制剂吡咯烷二硫基甲酸盐(PDTC)100μmol/L。检测心室收缩功能、乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)和心肌梗死面积。结果高铁血红素可明显改善缺血-复灌心脏的收缩功能,缩小心肌梗死面积,B组与A组比较差异均具有统计学意义(均P<0.01),而HO-1抑制剂ZnPP可显著抑制高铁血红素引起的HO-1活性增加,并取消高铁血红素诱导的心肌保护作用,C组与B组比较差异具有统计学意义(P<0.01)。C、D组与B组相比,心脏的收缩功能明显下降,心肌梗死面积增大,LDH和CK释放增加(均P<0.01)。结论高铁血红素可诱导心肌HO-1增加保护心肌缺血-复灌性损伤,其作用可被4,5,7-三羟基异丙酮或PDTC取消,PTK和NF-κB参与了高铁血红素的心肌保护机制。

蛋白酪氨酸磷酸酶1B及其小分子抑制剂的研究进展

蛋白酪氨酸磷酸酶1B(PTP-1B)是胰岛素和瘦素信号传导通路的负调节因子。目前,作为糖尿病和肥胖症治疗的新靶点,PTP-1B抑制剂的研究引起了广泛的关注。现从PTP-1B简介、生理功能以及抑制剂的结构性质等方面进行综述。

PTP-1B基因突变的PCR-RFLP与肥胖的相关性

采用多聚酶联反应-限制性片段长度多态性方法,对110例单纯肥胖者、110例肥胖合并2型糖尿病者、120例正常对照者PTP1B基因ISV5+3666、303位编码子进行酶切研究。结果显示PTP1B基因的P303P突变可能与肥胖发生相关,ISV5+3666delT突变与肥胖发生不相关。

PTP1B选择性抑制剂的分子动力学模拟及结合自由能计算

作为二型糖尿病的潜在治疗药物,蛋白质酪氨酸磷酸酯酶1B(PTP1B)的抑制剂研究一直备受关注.而其中一种二齿类抑制剂由于其普遍较高的选择性和活性,又是抑制剂的研究重点和热点.采用分子动力学方法取样,MM/GBSA方法计算了1个二齿类PTP1B抑制剂与PTP1B及其2个同家族酶TCPTP和SHP-2的结合自由能,得到了与实验活性值相符的结果.同时基于MM/GBSA的能量分解计算表明,抑制剂与PTP1B第2位点附近的2个残基ARG24和ARG254有很强的相互作用,与其他2个酶第2位点的相互作用则有所减弱,尤其是SHP-2,几乎没有实质性相互作用.这应该是抑制剂产生选择性的关键.同时活性位点附近的残基PHE182也与抑制剂分子有很强的相互作用,相比TCPTP也有很大优势.希望这些信息在进一步提升PTP1B抑制剂的选择性和活性方面提供帮助.

PTP-1B及其抑制剂与2型糖尿病的研究现状

蛋白酪氨酸磷酸酶-1B(PTP-1B)是蛋白酪氨酸磷酸酶(PTP)家族中的一员,在胰岛素信号转导途径中发挥重要作用。经研究发现,PTP-1B与2型糖尿病的发生、发展有密切关系。本文按PTP-1B小分子抑制剂的结构类别对近年来文献报道的代表性小分子PTP-1B抑制剂进行综述。表明深入研究PTP-1B及其有效的抑制剂对于2型糖尿病治疗具有良好的发展前景。

Extraction and PTP1B inhibitory activity of bromophenols from the marine red alga Symphyocladia latiuscula

Previously, we had characterized several structurally interesting brominated phenols from the marine red alga Symphyocladia latiuscula collected from various sites. However, Phytochemical investigations on this species collected from the Weihai coastline of Shandong Province remains blank. Therefore, we characterized the chemical constituents of individuals of this species collected from the region. Eight bromophenols were isolated and identified. Using detailed spectroscopic techniques and comparisons with published data, these compounds were identified as 2,3-dibromo-4,5-dihydroxybenzyl methyl ether (1), 3,5-dibromo-4-hydroxybenzoic acid (2), 2,3,6-tribromo-4,5-dihydroxymethylbenzene (3), 2,3,6-tribromo-4,5-dihydroxybenzaldehyde (4), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (5), bis(2,3,6-tribromo-4,5-dihydroxyphenyl)methane (6), 1,2-bis(2,3,6-tribromo-4,5-dihydroxyphenyl)-ethane (7), and 1-(2,3,6-tribromo-4,5-dihydroxybenzyl)-pyrrolidin-2-one (8). Among these compounds, 1 and 2 were isolated for the first time from S. latiuscula. Each compound was evaluated on the ability to inhibit protein tyrosine phosphatase 1B (PTP1B), which is a potential therapeutic target in the treatment of type 2 diabetes. Bromophenols 5, 6, and 7 showed strong activities with IC50 values of 3.9, 4.3, and 3.5 μmol/L, respectively. This study provides further evidence that bromophenols are predominant among the chemical constituents of Symphyocladia, and that some of these compounds may be candidates for the development of anti-diabetes drugs.

Synthesis of mangiferin derivates and study their potent PTP1B inhibitory activity

Protein tyrosine phosphatase 1 B （PTP1 B） has received considerable attention from the drug industry as a potential treatment for diabetes mellitus. Mangiferin has been reported to possess significant antidiabetic activity. Based on the previous study, eight new mangiferin derivates were synthesized and evaluated for their PTP1B inhibitory activity. Some of them displayed good inhibitory activity on PTP1B.

Isoprenylated Flavonoids with PTP1B Inhibition from Macaranga denticulata

Three new C-methylated and isoprenylated chalcone derivatives,dentichalcones A–C(1–3),together with six known compounds(4–9),were isolated from the twigs and leaves of Macaranga denticulata.Their structures were elucidated by spectroscopic analysis,including 1D,2D NMR,and MS data.The known compounds,(2E)-1-(5,7-dihydroxy-2,2,6-trimethyl-2H-benzopyran-8-yl)-3-(4-methoxyphenyl)-2-propen-1-one(4),(2E)-1-(5,7-dihydroxy-2,2-dimethyl-2H-benzopyran-8-yl)-3-phenyl-2-propen-1-one(5),laxichalcone(6),macarangin(7),bonanniol A(8),and bonannione A(9),showed inhibitory activities against protein tyrosine phosphatase 1B(PTP1B)in vitro.Graphical Abstract Three new C-methylated and isoprenylated chalcone derivatives,dentichalcones A–C(1–3),together with six known compounds,were isolated from the twigs and leaves of Macaranga denticulata.Some compounds showed inhibitory activities against PTP1B in vitro.

miR-362-3p通过MAPK1/PTEN/AKT信号通路调节冠心病大鼠心肌细胞凋亡和内皮细胞损伤

目的:通过构建冠心病大鼠模型,探讨微小RNA-362-3p(miR-362-3p)是否通过调节有丝分裂原活性蛋白激酶1(MAPK1)、蛋白酪氨酸磷酸酶基因(PTEN)、蛋白激酶B(AKT),参与影响冠心病大鼠的心肌细胞凋亡和内皮细胞损伤。方法:构建冠心病大鼠模型,随即将大鼠分为健康组、冠心病组、miR-362过表达组、过表达阴性对照组、过表达+MAPK1激活组,苏木精-伊红(HE)染色观察各组大鼠冠状动脉组织病理学变化;原位末端标记测定法(TUNEL)检测各组大鼠心肌细胞凋亡情况;酶联免疫吸附法(ELISA)检测血清中炎性相关因子及一氧化氮(NO)、内皮素(ET)-1等含量;蛋白免疫印迹法(Western Blot)检测各组大鼠冠状动脉组织中MAPK、磷酸化MAPK(p-MAPK)、PTEN、AKT、磷酸化AKT(p-AKT)信号通路蛋白表达水平。结果:健康组大鼠冠状动脉组织完好;与健康组比较,冠心病组大鼠冠状动脉组织增厚明显,心肌细胞凋亡率、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、ET-1含量及冠状动脉组织p-MAPK/MAPK、PTEN蛋白表达量升高,NO含量、p-AKT/AKT降低(P<0.05);与过表达阴性对照组比较,miR-362过表达组冠状动脉组织厚度减小,心肌细胞凋亡率及血清TNF-α、IL-1β、IL-6、ET-1含量、冠状动脉组织p-MAPK/MAPK、PTEN蛋白表达量降低,NO含量、p-AKT/AKT升高(P<0.05);与miR-362过表达组比较,过表达+MAPK1激活组冠状动脉组织增厚明显,且心肌细胞凋亡率、血清TNF-α、IL-1β、IL-6、ET-1含量及冠状动脉组织p-MAPK/MAPK、PTEN蛋白表达量升高,NO含量、p-AKT/AKT降低(P<0.05);冠心病组与过表达阴性对照组比较,各项指标比较差异无统计学意义(P>0.05)。结论:miR-362-3p过表达可调控MAPK1/PTEN/AKT信号通路,缓解内皮细胞损伤,减轻心肌组织损伤,从而改善冠心病病情。

神经调节蛋白-1对神经肌肉系统影响的研究进展

神经调节蛋白(NRG)家族对神经肌肉系统的发育和维持有重要作用,其中NRG-1被研究得最多,且与神经肌肉系统的关系也最为密切。NRG-1通过与细胞表面Ⅰ型酪氨酸激酶受体结合,促进神经肌肉系统的生长发育,并对各种病理条件下神经肌肉系统的损伤产生保护作用。磷脂酰肌醇-3-激酶/蛋白激酶B、过氧化物酶体增殖物激活受体/核因子κB等信号通路是NRG-1在细胞内发挥作用的主要信号通路。今后还需进一步开展临床转化研究,明确NRG-1是否可以应用于神经肌肉系统疾病患者。