标题：Ergosterol Ameliorates Diabetic Nephropathy by Attenuating Mesangial Cell Proliferation and Extracellular Matrix Deposition via the TGF-1/Smad2 Signaling Pathway
作者：Dong, Zhonghua; Sun, Yueyue; Wei, Guangwei; Li, Siying; Zhao, Zhongxi
作者机构：[Dong, Zhonghua; Sun, Yueyue; Zhao, Zhongxi] Shandong Univ, Sch Pharmaceut Sci, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China.; [Wei, G 更多
通讯作者：Zhao, ZX;Zhao, ZX
通讯作者地址：[Zhao, ZX]Shandong Univ, Sch Pharmaceut Sci, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China;[Zhao, ZX]Shandong Engn & Technol Res Ctr Juju 更多
关键词：ergosterol; diabetic nephropathy; mesangial cells; ECM; TGF-1
摘要：(1) Background: Diabetic nephropathy, a microvascular complication of diabetes, is one of the principal causes of end-stage renal disease worldwide. The aim of this study was to explore the therapeutic effects of ergosterol on diabetic nephropathy. (2) Methods: Streptozotocin (STZ)-induced C57BL/6 diabetic mice were treated with ergosterol (10, 20, 40 mg/kg/day) for 8 weeks by oral gavage. The in vitro study employed rat mesangial cells exposed to 30 mM glucose for 48 h in the presence of 10 or 20 M ergosterol. (3) Results: Ergosterol treatment improved body weights, ameliorated the majority of biochemical and renal functional parameters and histopathological changes, and reduced extracellular matrix (ECM) deposition in diabetic mice. In vitro, ergosterol suppressed proliferation, reduced the levels of ECM proteins, and increased the expression of matrix metalloproteinase-2 and -9 in high glucose-induced mesangial cells; Furthermore, ergosterol markedly improved transforming growth factor-1 (TGF-1) expression, enhanced phosphorylation levels of drosophila mothers against decapentaplegic 2 (Smad2), and regulated the downstream factors in vivo and in vitro. (4) Conclusions: Ergosterol alleviated mesangial cell proliferation and the subsequent ECM deposition by regulating the TGF-1/Smad2 signaling pathway.