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
邱文;车楠;周建博;李妍;赵聃;王迎伟
【期刊名称】《南京医科大学学报（自然科学版）》 【年(卷),期】2011(031)011
【摘要】Objective; To explore the roles of thrombospondin-1 (TSP-1) and transforming growth factor-β1 (TGF-β1) in mediat-ing the secretion of extracellular matrix (ECM) ,such as fibronectin (FN) and collagen Ⅳ,from rat glomerular mesangia] 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 CMC 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-pi 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-PI activation.%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collagenⅣ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18h,其FN和collagenⅣ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、collagenⅣ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、collagenⅣ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.
【总页数】7页(1543-1549)
【关键词】sublytic C5b-9;肾小球系膜细胞;血小板反应蛋白-1;转化生长因子-β1;纤维连接蛋白;Ⅳ型胶原蛋白
【作者】邱文;车楠;周建博;李妍;赵聃;王迎伟
【作者单位】南京医科大学微生物与免疫学系,江苏南京210029;南京医科大学微生物与免疫学系,江苏南京210029;南京医科大学微生物与免疫学系,江苏南京210029;南京医科大学微生物与免疫学系,江苏南京210029;南京医科大学微生物与免疫学系,江苏南京210029;南京医科大学微生物与免疫学系,江苏南京210029
【正文语种】中文 【中图分类】R692.3 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_journal-nanjing-medical-university-natural-sciences_thesis/0201245435448.html 【相关文献】
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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
