摘要
目的观察骨形态发生蛋白-7(BMP-7)对TGF-β1诱导人近端肾小管上皮细胞(HK-2)细胞外基质(ECM)成分表达的影响,以探讨其延缓肾间质纤维化病变的作用机制。方法将体外培养的HK-2细胞分为空白对照组,3μg.L-1TGF-β1组,BMP-7组,TGF-β1加不同浓度BMP-7组。免疫荧光检测FN的表达;RT-PCR和Western blot分别检测FN、ColⅠα1mRNA及蛋白的表达。结果免疫荧光检测结果显示,3μg.L-1TGF-β1刺激HK-2细胞48h后,FN表达明显增强;加入200μg.L-1BMP-7干预后荧光明显减弱。RT-PCR和Western blot结果显示,TGF-β1刺激HK-2细胞48h后,FN、ColⅠα1mRNA及蛋白表达均明显高于对照组(P<0.01);BMP-7(100～400μg.L-1)可在mRNA及蛋白水平呈剂量依赖性下调TGF-β1诱导的FN、ColⅠα1的表达。结论BMP-7能抑制TGF-β1诱导的HK-2细胞FN、ColⅠα1的合成。表明BMP-7抑制肾小管间质纤维化的进展、改善肾功能的作用,部分是通过抑制肾小管上皮细胞分泌细胞外基质实现的。
Aim To investigate the effects of bone morphogenic protein （BMP）-7 on the expression of extracelluar matrix components （Col I and FN） in human renal proximal tubular cells（ HK-2 ） induced by transforming growth factorq31 （ TGF-β1 ）, and to explore the inhibition of BMP-7 on renal interstitial fibrosis. Methods HK-2 cells were treated with TGF-β1 , BMP-7, or a combination of both for 48 h. The expression of FN was assessed by indirect immunofluorescence. RT-PCR and Western blot were used to determine the mRNA and protein expression of FN and Col I α1. Results Indirect immunofluorescence staining showed that FN staining in 3 μg · L^-1 TGF-β1 group was considerably stronger than that in control group. By an addition of200 μg · L ^-1 BMP-7, the expression of FN was significantly inhibited. RT-PCR and Western blot showed the mRNA and protein expression of FN and Col I α1 were up-regulated by TGF-β1 after 48 hours significantly （P 〈0. 01 ）. BMP-7 dramatically down-regulated the expression of FN and Col I α1 induced by TGF-β1 in a dose-dependent manner both in mRNA and protein levels. Conclusions BMP-7 has the role to inhibit the.overproduction of FN and Col I α1 induced by TGF-β1. BMP-7 exerts its antifibrotic effect partially through blocking the TGF-β1-induced accumulation of ECM in human renal tubular epithelial cells.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第11期1453-1457,共5页
Chinese Pharmacological Bulletin
基金
福建省自然科学基金资助项目(NoC0710009)
关键词
骨形态发生蛋白质类
转化生长因子Β
上皮细胞
细胞外基质
bone morphogenetic proteins
transforminggrowth factor-β
epithelial cells
extracellular matrix
