Zhang Shukun, Zhang Menglan, Huang Hong, Zhou Shiying, Du Yanshneg, Yi Xin, Luo Junming
Department of Pathology, Qinghai Provincial People's Hospital, 2 Gonghe Road, Xining, Qinghai 810007, China.
Medical College of Qinghai University, 16 Kunlun Road, Xining 810000, China.
Biochem Biophys Res Commun. 2016 May 27;474(2):303-308. doi: 10.1016/j.bbrc.2016.04.091. Epub 2016 Apr 20.
This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-β1) inhibitors and TGF-β1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-β1/Smad3 signaling pathway. Our data demonstrated that Matrilin-2 expression was markedly induced by high glucose and TGF-β1. High glucose-induced Matrilin-2 expression was inhibited by TGF-β1/Smad3 inhibitors, indicating that Matrilin-2 was markedly induced by high glucose and this induction was mediated by the TGF-β1/Smad3 pathway. Taken together, our results showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN.
本研究旨在利用小鼠系膜细胞系评估高糖对细胞外基质(ECM)蛋白Matrilin-2表达的影响及其作用机制。将小鼠系膜细胞(MMCs)培养于含有正常浓度(5 mM d-葡萄糖)或高浓度葡萄糖(30 mM d-葡萄糖)的培养基中。通过RT-PCR或蛋白质印迹法评估Matrilin-2的表达。此外,使用转化生长因子β1(TGF-β1)抑制剂和TGF-β1来确定葡萄糖调节的Matrilin-2表达是否由TGF-β1/Smad3信号通路介导。我们的数据表明,高糖和TGF-β1均可显著诱导Matrilin-2表达。TGF-β1/Smad3抑制剂可抑制高糖诱导的Matrilin-2表达,这表明高糖可显著诱导Matrilin-2表达,且这种诱导作用由TGF-β1/Smad3通路介导。综上所述,我们的结果表明,由TGF-β1/Smad3信号通路介导的高糖诱导的Matrilin-2表达可能在糖尿病肾病(DN)发病机制中起作用,我们的发现为DN提供了一个潜在的诊断和/或治疗靶点。