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姜大朋,李昭铸,蒋志涛,刘君阳,李天竹,王 娜.肝细胞生长因子阻抑TGF-β1诱导大鼠韧带成纤维细胞?琢-SMA过表达及其机制[J].中国康复医学杂志,2009,24(10):906~909
肝细胞生长因子阻抑TGF-β1诱导大鼠韧带成纤维细胞?琢-SMA过表达及其机制    点此下载全文
姜大朋  李昭铸  蒋志涛  刘君阳  李天竹  王 娜
哈尔滨医科大学附属第二医院小儿外科,150086
基金项目:黑龙江省自然科学基金项目(D200618);国家自然科学基金青年基金项目(30901516)
DOI:
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摘要:
      目的:研究肝细胞生长因子(HGF)能否阻抑TGF-β1诱导的大鼠内侧副韧带(MCL)成纤维细胞?琢-SMA过表达及其可能涉及的信号传导通路。方法:采用组织块培养法培养大鼠MCL成纤维细胞,培养液中加入TGF-β1(5ng/ml)及HGF (10—40 ng/ml)。培养72h后,用RT-PCR检测各组?琢-SMA mRNA及Smad3 mRNA的变化;细胞免疫组化检测?琢-SMA蛋白的表达。结果:TGF-β1能显著诱导?琢-SMA及Smad3的表达(P<0.01),而HGF则可以有效地阻抑其表达,其效应呈剂量依赖性(P<0.05)。结论:HGF可以通过下调Smad3的表达来阻抑TGF-β1诱导的?琢-SMA过表达。这为利用HGF预防和治疗MCL损伤后瘢痕及纤维化在细胞和分子水平提供了依据。
关键词:肝细胞生长因子  转化生长因子-β  内侧副韧带  成纤维细胞  ?琢-平滑肌肌动蛋白
Hepatocyte growth factor suppresses the overproduction of α-SMA induced by TGF-β1 in rat medial collateral ligament fibroblasts    Download Fulltext
Department of Pediatric Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086
Fund Project:
Abstract:
      Objective:To examine the effectiveness of HGF in blocking TGF-β1-induced ?琢-SMA production in rat medial collateral ligament (MCL) fibroblasts. Method:Fibroblasts were obtained from rat MCL. Cell culture was supplemented with 5ng/ml of TGF-β1 along with increasing doses of HGF (10-40 ng/ml). After 72 hours incubation, the productions of ?琢-SMA and Smad3 mRNA were assayed by RT-PCR. Expression of ?琢-SMA protein was assessed by immunostaining. Result:Treatment with TGF-β1 significantly stimulated ?琢-SMA and Smad3 mRNA production in MCL fibroblasts (P<0.01). Remarkably, the addition of HGF reduced productions of all components induced by TGF-β1 in a dose-dependent manner (P<0.05). Conclusion:HGF antagonizes TGF-β1 induced ?琢-SMA production in MCL fibroblasts by down regulating Smad3. The findings provide a cellular and molecular basis for HGF′s acting as a therapeutic agent for MCL scar and fibrosis formation.
Keywords:hepatocyte growth factor  transforming growth factor-β  medial collateral ligament  fibroblast  ?琢-smooth muscle actin
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