Sublytic C5b-9诱导肾小球系膜细胞产生的TSP-1和TGF-β1对其合成FN和collagen Ⅳ的影响
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国家自然科学基金资助(31000396, 81072402);江苏省高校自然科学研究(10KJB310006);南京医科大学科技发展基金面上项目(09NJMUM003);南京医科大学基础医学院青年教师培养基金(09JC007)


The effects of TSP-1 and TGF-β1 induced by sublytic C5b-9 on FN and collagen IV synthesis from glomerular mesangial cell
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    摘要:

    目的:探讨亚溶解型(sublytic)C5b-9复合物刺激大鼠肾小球系膜细胞(glomerular mesangial cell,GMC)后,诱生的血小板反应蛋白-1(thrombospondin-1,TSP-1)与转化生长因子-β1(transforming growth factor-β1,TGF-β1)对其促进细胞外基质(extracellular matrix,ECM),如纤维连接蛋白(fibronectin,FN)和 Ⅳ 型胶原蛋白(collagen Ⅳ)合成的影响-方法:体外培养大鼠GMC,进行不同分组处理并给予sublytic C5b-9刺激,然后分别检查受刺激的GMC合成TSP-1和TGF-β1因子水平,同时检测GMC分泌FN和collagen Ⅳ的水平-此外,应用人工合成的TSP-1封闭肽段(GGWSHW)和TGF-β1中和抗体处理培养的大鼠GMC,研究TSP-1和TGF-β1在sublytic C5b-9诱导的GMC分泌上述ECM中的作用及其相互关系-结果:培养的大鼠GMC在sublytic C5b-9刺激后18 h,其FN和collagen Ⅳ表达水平均明显升高-同时,TSP-1蛋白表达和TGF-β1分泌(包括活化的TGF-β1含量)也显著增多-用TSP-1封闭肽段(GGWSHW)处理大鼠GMC后亦能显著抑制由sublytic C5b-9诱导的TGF-β1活化,并减少FN-collagen Ⅳ的产生-同样用TGF-β1中和抗体处理GMC后也能明显抑制由sublytic C5b-9导致的FN-collagen Ⅳ的分泌-结论:体外用sublytic C5b-9刺激大鼠GMC,能诱导其ECM分泌与TSP-1和TGF-β1的合成及活化,而sublytic C5b-9促进GMC分泌ECM的机制可能与其诱导TSP-1合成及活化的TGF-β1存在一定的关系-

    Abstract:

    Objective: To explore the roles of thrombospondin-1 (TSP-1) and transforming growth factor-β1 (TGF-β1) in mediating the secretion of extracellular matrix (ECM),such as fibronectin (FN) and collagen Ⅳ,from rat glomerular mesangial cell (GMC) induced by sublytic C5b-9 complexes. Methods: Rat GMC was cultured and divided into different groups. The expression levels of TSP-1 and TGF-β1 as well as FN and collagen Ⅳ in GMC with sublytic C5b-9 stimulation were measured. In addition,the synthetic blocking peptide of TSP-1(GGWSHW) and TGF-β1 neutralizing antibody were utilized to explore the role of TSP-1 and TGF-β1 in ECM secretion from GMC induced by sublytic C5b-9,as well as the relationship between TSP-1 and TGF-β1. Results: The protein levels of FN and collagen Ⅳ as well as TSP-1 and TGF-β1 including the activated TGF-β1 were significantly increased in rat GMC at 18 h after sublytic C5b-9 stimulation. The blocking peptides of TSP-1 (GGWSHW) could significantly inhibit TGF-β1 activation and reduce the production of FN and collagen Ⅳ. In addition,TGF-β1 neutralizing antibody could also obviously inhibit the expression of FN and collagen Ⅳ in GMC upon sublytic C5b-9 attack. Conclusion: Sublytic C5b-9 can promote ECM secretion and TSP-1 and TGF-β1 production as well as TGF-β1 activation in rat GMC in vitro,while the secretion of ECM stimulated by sublytic C5b-9 is possibly mediated in part by TSP-1-regulated TGF-β1 activation.

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邱 文,车 楠,周建博,李 妍,赵 聃,王迎伟. Sublytic C5b-9诱导肾小球系膜细胞产生的TSP-1和TGF-β1对其合成FN和collagen Ⅳ的影响[J].南京医科大学学报(自然科学版),2011,(11):1543-1549

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  • 收稿日期:2011-07-02
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