Role of Insulin-like Growth Factor II Receptor in Transdifferentiation of Free Silica-induced Primary Rat Lung Fibroblasts

Objective To study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts Methods Rat lung fibroblasts and rat alveolar macrophages were cultured. A transdifferentiation model of primary rat lung fibroblasts was induced by free silica. Levels of a-SMA protein, IGF-liR protein and mRNA were measured by immunocytochemistry, Western blot and RT-PCR, respectively. Lung fibroblasts were treated with Wortmannin. Results The expression levels of a-SMA concentration and decreased after Wortmann and IGF-IIR increased with the increasing free silica n was used. Conclusion The IGF-IIR plays an important role in free silica-induced transdifferentiation of primary rat lung fibroblasts.

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

Expression of insulin-like growth factor Ⅱ and its receptor in hepatocellular carcinogenesis

INTRODUCTIONInsulin-like growth factor Ⅱ(IGF-Ⅱ) is a mitogenic peptide of 74 kD and is mostly synthesized in fetal liver tissue .IGF-Ⅱ is believed to play an important role in fetal growth and development and is involved in cellular proliferation and differentiation[1-5]. Recently ,several researchers have reported increased expression of the IGF-Ⅱgene in human hepatocellular carcinoma (HCC) and adjacent non-cancerous liver tissues [6-10].

SIMULTANEOUS OVER-EXPRESSION OF INSULIN-LIKE GROWTH FACTOR- Ⅱ (IGF- Ⅱ ) AND IGF- Ⅱ RECEPTOR(IGF- Ⅱ R) GENES IN HUMAN PRIMARY CANCER-IMPLICATION OF AUTOCRINE AND PARACRINE MECHANISM IN AUTONOMOUS GROWTH OF HEPATIC CANCER

This is first report about the simultaneous over-expression of both Insulin-like growth factor (IGF- I ) and its receptor (IGF- I R) at mRNA level in human primary hepatic Cancer (PHC). In 10 PHC samples from China, IGF-I and IGF- I R were both over-expressed, whereas only a background signal was detected in normal liver. In 5 pairs of PHC and its non- tumorous adjacent liver tissues from South Africa, IGF- I and IGF- I R were also over-expressed in PHC. mRNA expression of IGF- I in all 5 cases and IGF- I R in 4 of 5 cases were higher in cancer than non- tumorous adjacent liver tissues. These results strongly implicate that an autocrine and/ or paracrine mechanism might be Involved in formation and progression of PHC.

RNA interference affects tumorigenicity and expression of insulin-like growth factor-1,insulin-like growth factor-1 receptor,and basic fibroblast growth factor-2 in rat C6 glioma cells

BACKGROUND： Human gliomas are more likely to express basic fibroblast growth factor-2 （FGF-2） insulin-like growth factor-1（IGF-1）, and IGF-1 receptor （IGF-1R） than normal brain tissue. These factors activate signal transduction systems of Ras/MAPK and PI3K/Akl, which promote glioma growth. OBJECTIVE： To utilize RNA interference （RNAi） technique to down-regulate FGF-2, IGF-1, and IGF-1R gene expression, and to investigate the effects of these genes on rat C6 glioma cells, as well as the feasibility of RNAi for treating glioma. DESIGN, TIME AND SETTING： This neurooncological, randomized, controlled, in vivo and in vitro experiment, which used RNAi methodology, was performed at the Laboratory of Molecular Biology, Institute of Biochemistry, Chinese Academy of Sciences between August 2005 and February 2008. MATERIALS： Rat C6 cell lines were purchased from Shanghai Institute of Cellular Biology Affiliated to Chinese Academy of Sciences. Small interfering RNA （siRNA） was synthesized by Shanghai GenePharma. Anti-IGF-1, anti-IGF-1R, anti-FGF-2, anti-mouse and anti-rabbit IgG G1-HRP antibodies were provided by Santa Cruz Biotechnology, USA. Four to six week-old BALB/c nude mice were purchased from the Laboratory Animal Center, Chinese Academy of Sciences. METHODS： C6 glioma cells were transfected with siRNA, which was chemically synthesized in vitro to correspond to endogenous FGF-2, IGF-1, and IGF-1R genes. The inhibition ratio of targeting mRNA expression was detected by semiquantitative RT-PCR, and protein expression was determined by Western blot analysis. C6 glioma cell proliferation was observed using a growth curve C6 glioma cell apoptosis rate and cell cycle were detected by flow cytometry. C6 glioma cell growth regression was observed by transwell migration assay. In addition, nude mouse subcutaneous tumor models were used in this study. For studying the anti-tumor effects of IGF-1 and IGF-1R siRNA, two blank control groups, with six mice each, were set up： A （2.5 μg siRNA was injected one week after C6 cells were inoculated, Le., when tumor volume reached 8 mm × 8 mm） and B （siRNA was injected at the same time with C6 cells were inoculated. To study the effects of FGF-2 siRNA, the groups consisted of a blank control group, negative control group, 2.6 μg siRNA group, 4 μg siRNA group, and 5.3 μg siRNA group, with six mice each. MAIN OUTCOME MEASURES： mRNA and protein inhibition ratio of FGF-2, IGF-1, and IGF-1 R; C6 glioma cell proliferation, apoptosis, and cycle growth arrest; C6 glioma cell growth regression and subcutaneous tumorigenicity rates. RESULTS： All siRNA constructs proved to be effective. After 48 hours, transfection of 200 nmol/L siRNA resulted in a FGF-2 or IGF-1R gene inhibition ratio 〉 80% and an IGF-1 gene inhibition ratio of approximately 70%. Protein expression levels for FGF-2, IGF-1, and IGF-1R decreased in a dose-dependent manner following siRNA transfection, with an inhibition rate 〉 85%, 60%, and 50%, respectively. C6 glioma cell proliferation and apoptosis rates increased in proportion to siRNA. The apoptosis rate of C6 glioma cells induced by FGF-2, IGF-1, and IGF-1R siRNA was 39.96%, 15.07% and 22.47%, respectively （P 〈 0.01）. Transfection of 200 nmol/L IGF or IGF-1R siRNA for 48 hours suppressed C6 glioma cell migration. At 30 days after intratumoral injection of 2.6, 4, and 5.3 tJg FGF-2 siRNA, tumor growth regression rate of FGF-2 siRNA was 56%, 67%, and 86%, respectively. The tumor growth regression rate was 71.88% and 45.71%, respectively, when IGF-1 or IGF-1R siRNA was intratumorally injected 1 week after C6 glioma cell transplantation. When IGF-1 or IGF-1 R siRNA was intratumorally injected during C6 glioma cell transplantation, the tumor growth regression rate was 78.13% and 74.29%, respectively. CONCLUSION： siRNA transfection downregulated gene expression of FGF-2, IGF-1, and IGF-1R In addition, siRNA treatment markedly suppressed glioma cell proliferation, growth, and migration, and concomitantly reduced subcutaneous tumorigenicity.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type Ⅱ receptor

BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

Epigenetic regulation of insulin-like growth factor axis in hepatocellular carcinoma

The insulin-like growth factor(IGF) signaling path-way is an important pathway in the process of hepa-tocarcinogenesis,and the IGF network is clearly dysregulated in many cancers and developmental abnormalities.In hepatocellular carcinoma(HCC),only a minority of patients are eligible for curative treatments,such as tumor resection or liver transplant.Unfortunately,there is a high recurrence of HCC after surgical tumor removal.Recent research efforts have focused on targeting IGF axis members in an attempt to find therapeutic options for many health problems.In this review,we shed lights on the regulation of members of the IGF axis,mainly by micro RNAs in HCC.Micro RNAs in HCC attempt to halt the aberrant expression of the IGF network,and a single micro RNA can have multiple downstream targets in one or more signaling pathways.Targeting micro RNAs is a relatively new approach for identifying an efficient radical cure for HCC.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

EXPRESSION OF INSULIN-LIKE GROWTH FACTOR Ⅱ(IGF-Ⅱ)IN HUMAN HEPATOCELLULAR CARCINOMA AND LIVER CIRRHOSIS:ITS RELATIONSHIP WITH HEPATITIS B VIRUS X PROTEIN EXPRESSION

Sixty cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry method using antibodies against IGF-II and HBxAg on formalin-fixed, paraffin-embedded tissue sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-II were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-II was positive in 23 HCC (83.1%) and 6 LC (60%). The positive expression rates of IGF-II in HBxAg positive tissues were significantly higher than those in HBxAg negative tissues (P<0.05). There were three types of distribution of IGF-II expression in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) inside nucleus. IGF-II was highly expressed in most of hyperplastic and neoplastic nodules hepatocytes and some of regeneration nodules. Small polygonal liver cells (SPLCs) were found in the liver tissues surrounding the tumor and cirrhosis and they were positive to both IGF-II and HBxAg. The positive rates of IGF-II in SPLC were 86.4% (38/44) in the HBxAg-positive tissues and 40.5%, (15/37) in the HBxAg-negative tissues. The above findings suggest that IGF-II plays an important role in abnormal proliferation of HCC and SPLC. The relation between IGF-II andHBxAg and the nature of SPLCs are also discussed.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Effect of recombinant growth hormone on expression of growth hormone receptor, insulin-like growth factor mRNA and serum level of leptin in growing pigs

Sixteen Large White ?Landrace castrated male pigs were allotted into treatment and control group. The treatment group was injected intramuscularly with recombinant porcine growth hormone (rpGH, 4 mg·d-1) and the control group with vehicle for 28 days. Animals were slaugh-tered 4 h after final injection for liver, longissimus dorsi (LD) muscle and blood sampling. Serum concentration of insulin-like growth factor 1 (IGF-I) and leptin were determined by RIA. The total RNA was extracted from tissues to measure the abundance of growth hormone receptor (GHR), IGF-I mRNA by RT-PCR with 18S rRNA internal standard. Results showed that rpGH enhanced the average daily weight gain by 26.1% (P < 0.05), the serum IGF-I concentration by 70.94% (P < 0.01), decreased serum leptin by 34.8% (P < 0.01). The relative abundance of GHR and IGFmRNA in liver were increased by 24.45% (P < 0.05) and 45.30% (P < 0.01), respectively, but no difference of GHR (P > 0.05) and IGF-I mRNA (P > 0.05) in LD between GH treated and control group was found. These results suggest that rpGH can up-regulate hepatic GHR and IGF-I gene expression and improve animal growth. However the effect of rpGH on GHR and IGF-I gene ex-pression are tissue-specific.

Pancreatic neuroendocrine tumor with hypoglycemia and elevated insulin-like growth factor II:a case report

Pancreatic neuroendocrine tumors(pNETs)can be associated with different clinical syndromes.Insulinoma is the most common functioning pNET characterized by hypoglycemia and hyperinsulinemia.The authors report a case of a man presenting with hypoglycemia and biochemical features of insulinoma.A pancreatic lesion was found and growth hormone(GH)deficiency was also diagnosed associated with an empty sella present on the pituitary magnetic resonance imaging.The disappearance of hypoglycemia and normalization of GH secretion after surgical resection of the pancreatic lesion,revealed a rare pNET secreting insulin-like growth factor II.

丝裂素活化蛋白激酶参与AngII诱导心肌细胞血小板衍生生长因子受体的表达

目的 探讨丝裂素活化蛋白激酶在血管紧张素II(AngII)诱导心肌细胞血小板衍生生长因子受体 - β(PDGF - β)表达中的作用。 方法 分离纯化培养的乳鼠心肌细胞 ,以10 -7mol·L-1AngII刺激为AngII组 ;以 10 -5mol·L-1PD980 5 9(一种丝裂素活化蛋白激酶抑制剂 )预孵育 30min10 -7后再用AngII刺激为PD980 5 9组 ,以正常的乳鼠心肌细胞为对照组 ;免疫印迹法测定培养 2 4h时心肌细胞PDGF - β受体的含量。 结果 AngII刺激培养 2 4h的乳鼠心肌细胞PDGF - β受体表达增强 (P <0 .0 5 ) ,PD980 5 9可部分抑制AngII对PDGF - β受体表达的诱导作用。结论 丝裂素活化蛋白激酶参与AngII上调心肌细胞PDGF -

肝癌、癌旁肝组织IGF-Ⅱ、IGF-Ⅱ受体及CSF-1受体/c-fms癌基因产物的表达

本文采用免疫组织化学(ABC)法、Western印迹法和Northern印迹法从细胞、蛋白及转录水平观察17例肝癌及癌旁肝组织中IGF-Ⅱ、IGF-Ⅱ受体和CSF-1受体/c-fms癌基因产物的表达。结果表明,肝癌组织中3种基因产物的表达水平显著高于正常肝组织;癌旁肝组织中IGF-Ⅱ和IGF-Ⅱ受体的表达水平显著高于肝癌组织;肝癌及癌旁肝组织IGF-Ⅱ基因呈胚胎型表达特点。但是,肝癌组织中CSF-1受体基因表达则显著高于癌旁肝组织。由此提示3种基因产物异常的过量表达与肝癌细胞自分泌生长刺激机制有关。

联合应用TGF-β、TGF-βR siRNA对小鼠急性肝损伤TGF-β/Smad信号传导通路相关基因表达的抑制

目的:探讨TGF-β1、TGF-β1RsiRNA联合应用对小鼠急性肝损伤TGF-β/Smad信号传导通路的干预作用.方法:清洁级健康大鼠36只分为2组:正常对照组(n=6,注射生理盐水)与实验组(n=30).实验组动物在实验第1天和第5天腹腔注射CCl4花生油溶液6mL/kg,造成急性肝损伤并启动TGF-β/Smad信号传导通路.实验分为TGF-β1shRNA干预组(T);TGF-β1siRNA+TβRⅠshRNA干预组(T+R1);TGF-β1shRNA+TβRⅡsiRNA干预组(T+R2);TGF-β1siRNA+TβRⅠshRNA+TβRⅡshRNA干预组(T+R1+R2)和模型对照组(M).观察各实验组血清ALT、AST、HA;肝组织学RT-PCR和免疫组织化学检测肝组织中α-SMA、COL-1、COL-3、TGF-β1、Smad3、PCNA和TGF-αmRNA及蛋白的表达.结果:经shRNA质粒DNA干预的4个治疗组与模型组比较,均能显著降低血清ALT,AST及HA的水平(ALT:592.80±98.4IU/L,440.80±91.9IU/L,461.61±120.0IU/L,284.00±49.0IU/Lvs949.5±196.1IU/L;AST:686.80±112.3IU/L,591.00±99.87IU/L,607.50±84.8IU/L,398.30±61.9IU/Lvs985.67±274.8IU/L;HA:5682.80±824.14μg/L,2871.26±394.68μg/L,3004.29±354.25μg/L,1982.12±402.71μg/Lvs8444.65±812.15μg/L,P<0.05)的测定值;4个治疗组两两比较,T+R1+R2组疗效明显高于其他3组(P<0.01).与模型组比较.shRNA质粒DNA干预能明显抑制TGF-β1,Smad3,α-SMA,COL-1及COL-3的mRNA与蛋白的表达(均P<0.05).其抑制效果以T+R1+R2组最明显.对蛋白水平表达的作用也有相似趋势.结论:针对TGF-βRⅠ及其Ⅰ型受体(TβRⅠ)、Ⅱ型受体(TβRⅡ)的siRNA联合治疗对小鼠肝损伤中TGF-β/Smad信号传导通路相关的基因表达的抑制具有协同作用.

人VEGF受体Ⅱ胞外Ⅲ区单克隆抗体研制与生物学活性测定

根据GenBank中发表的血管内皮细胞生长因子(VEGF)受体Ⅱ(KDR)基因序列,设计1对引物经RT-PCR从人脐静脉内皮细胞中克隆出KDR胞外Ⅲ区(KDRD3)编码序列,克隆入原核表达载体pGEX-6P1。重组质粒转化大肠杆菌BL21,用IPTG于37℃条件下诱导,经SDS-PAGE和Western blotting分析,表达出的融合蛋白大小为33.4 ku。利用纯化的重组融合蛋白免疫BALB/c小鼠,经淋巴细胞杂交瘤技术筛选获得2株KDR特异性单克隆抗体C4和F6。2株单抗均能特异性识别HUVEC细胞表达的天然KDR分子,HUVEC迁移抑制试验和HUVEC体外血管形成抑制试验结果显示,2株单抗均能特异性阻断血管内皮细胞生长因子与KDR分子的相互作用。结果表明:所获得的2株单抗对KDR具有良好的特异性和中和活性。

TGFβ_1及其受体在大鼠整胚及软骨雏形发育过程中的表达

目的观察TGFβ1及TβRⅠ、TβRⅡ在大鼠整胚及软骨雏形中的表达,初步探讨它们与大鼠整胚及软骨雏形发育间可能的相互关系和作用机制。方法半定量RT-PCR分析3种因子在13～17d全胚中的变化情况;免疫组化法观察3种因子在13～17d软骨雏形中的表达及该组织发育结构特点。结果半定量RT-PCR显示,3种因子在发育13～15d表达呈递增趋势,16～17d出现下降。免疫组化显示,TGFβ1主要位于软骨雏形内的软骨骨祖细胞,TβRI、TβRII即可位于软骨骨祖细胞内,也可位于软骨外周的膜上及软骨雏形周围的间质内。结论 TGFβ1及TβRⅠ、TβRⅡ在大鼠整胚及软骨雏形发育过程中可能起着重要的调控作用,尤其是对组织器官形态的发生。

孕期咖啡因暴露所致雌性子代胎鼠肾脏宫内发育迟缓及其发生机制

目的观察孕期咖啡因暴露(PCE)♀胎肾发育病理学变化和皮质酮(CORT)处理对原代后肾间充质细胞基因表达的影响,探究PCE影响胎鼠肾脏发育的可能机制。方法受孕Wistar大鼠于孕9-20 d(GD 9-20)经口灌胃咖啡因(30、120 mg·kg^(-1)·d^(-1)),孕鼠于GD20处死,取♀胎鼠并收集肾脏,检测肾脏病理学变化和基因表达;在原代后肾间充质细胞上给予不同浓度CORT(250、500、1 000μg·L^(-1))处理24 h,检测细胞基因表达。结果与对照组相比,PCE组♀胎肾肾小球的球囊空虚,鲍曼囊腔变大,毛细血管网发育不良,GDNF/c-Ret信号通路抑制;CORT处理原代后肾间充质细胞下调AT_1R/AT_2R及GDNF/c-Ret信号通路的表达。结论 PCE♀胎鼠肾脏发育不良,其机制与PCE所致高血CORT下胎肾局部AT_1R/AT_2R及GDNF/c-Ret信号通路的表达抑制有关。

糖尿病大鼠肾脏TGF-β受体蛋白表达的实验研究

目的：探讨持续高血糖对糖尿病大鼠肾脏转化生长因子βⅠ型受体(TGFβRⅠ)和转化生长因子βII型受体(TGFβRII)蛋白表达的影响。方法：雄性Wistar大鼠20只随机分为正常对照组（C组）和糖尿病组（D组），实验第9周用免疫组化和图像分析系统检测两组肾脏TGFβRI和TGFβRII蛋白表达水平。结果：与对照组相比，糖尿病组TGFβRI和TGFβII蛋白表达分别增加100%和118%（P<0.01）。结论：持续高血糖显著增加糖尿病大鼠肾脏TGFβRI和TGFβRII受体蛋白表达，可能对糖尿病肾病的发生发展发挥重要作用。

IGF-Ⅰ和IGF-Ⅱ在子宫肌瘤患者血清中的水平及其与肿瘤组织ER、PR表达的相关性分析

目的:探讨胰岛素样生长因子(IGF)-Ⅰ和IGF-Ⅱ在子宫肌瘤患者血清中的水平及其与肿瘤组织雌激素受体(ER)、孕激素受体(PR)表达的相关性。方法:选取2014年9月至2015年8月青岛大学附属青岛妇女儿童医院收治的84例子宫肌瘤患者为研究组,另选取同期在本院行健康体检的84例健康妇女为对照组。采用酶联免疫吸附试验(ELISA)法检测两组外周血IGF-Ⅰ和IGF-Ⅱ水平,免疫组化法检测研究组肿瘤组织ER、PR的表达,分析IGF-Ⅰ和IGF-Ⅱ与患者肿瘤组织中的ER、PR表达的相关性。结果:研究组血清IGF-Ⅰ和IGF-Ⅱ水平均明显高于对照组(均P<0.01);ER(+)、PR(+)患者血清中IGF-Ⅰ和IGF-Ⅱ水平均显著高于ER(-)、PR(-)患者(均P<0.01);Pearson相关性分析结果显示,子宫肌瘤患者血清IGF-Ⅰ和IGF-Ⅱ水平与子宫肌瘤组织中ER、PR表达均呈正相关关系(均P<0.01)。结论:子宫肌瘤患者血清中的IGF-Ⅰ和IGF-Ⅱ水平升高,两者与肿瘤组织ER、PR的表达呈正相关关系,并可能影响子宫肌瘤的发生和发展。