糖尿病肾病(DN)已成为导致慢性肾衰竭的主要原因，其发病机制仍未充分阐明，且尚无有效治疗措施。SnoN是TGF-β1/Smads通路的负调节因子，而肾小管上皮细胞SnoN蛋白表达减少可能是DN肾纤维化进行性发展的重要因素。BMP-7具有对抗TGF-β1致纤维化的效应，但其作用机制尚不明确。我们近期的研究提示，恢复内源性SnoN蛋白表达水平可能是BMP-7抗TGF-β1致肾纤维化效应的重要机制。但在DN时，BMP-7调控SnoN表达的具体作用环节和机制尚不清楚。本项目以db/db小鼠和体外高糖培养的肾小管上皮细胞为研究对象，分别在体内和体外予以BMP-7干预，采取基因敲降、过表达及抑制实验干预Smad1/5、ERK1/2通路，从基因转录和蛋白稳定性两个方面，探讨BMP-7上调SnoN表达的具体调控环节和机制，以期进一步认识DN肾小管-间质纤维化的发病机制，探寻新的有效治疗靶点。

Diabetic nephropathy (DN) has become a major cause of chronic renal failure, but the pathogenesis of DN is dimly known and without effective treatment. SnoN, as a negative regulator of TGF-β1/Smads pathway, which protein expression reduced with the development of renal fibrosis accelerates pathogenesis. Bone morphogenetic protein-7(BMP-7) contributes to resist the effects of fibrosis TGF-β1 induced, but the mechanism is in a dilemma.Our recent studies indicated that restoring the protein level of endogenous SnoN may be an important mechanism referred to the effects of BMP-7 against renal fibrosis TGF-β1 mediated. But at present, it remain unknown that BMP-7 mediated patterns and molecular mechanism of action emphasis on regulation of SnoN expression in DN. db/db mice and renal tubular epithelial cells under high-glucose cultivation as the research object, we intend to treat with exogenous hBMP-7 in vivo and in vitro respectively, and apply knockdown or over-expression of gene and inhibition of Smad1/5 and ERK1/2 pathways to explicit the patterns and the molecular mechanism involved in regulation of SnoN expression BMP-7 mediated, based on two aspects of gene transcription and protein stability. In order to further elucidate the pathogenesis of tubulointerstitial fibrosis, for purpose of providing the new targets for the effective treatment of DN.