Fenofibrate attenuated glucose-induced mesangial cells proliferation and extracellular matrix synthesis via PI3K/AKT and ERK1/2.
Fenofibrate attenuated glucose-induced mesangial cells proliferation and extracellular matrix synthesis via PI3K/AKT and ERK1/2.
复制标题
非诺贝特通过 PI3K/AKT 和 ERK1/2 减弱葡萄糖诱导的系膜细胞增殖和细胞外基质合成。
DOI：
10.1371/journal.pone.0076836
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yao Y
中科院分区：
文献类型：
--
作者：
Zeng R;Xiong Y;Zhu F;Ma Z;Liao W;He Y;He J;Li W;Yang J;Lu Q;Xu G;Yao Y
系膜细胞外基质（ECM）和系膜细胞增生是糖尿病肾病（DN）的主要病理特征。非诺贝特是一种过氧化物酶体增殖物激活受体α激动剂，已被证明可减少糖尿病肾病细胞外基质的形成。然而，这种影响的机制仍有待阐明。本研究采用MTT法、流式细胞术和Western blot法研究了非诺贝特对高糖诱导的大鼠系膜细胞增殖和细胞外基质释放的影响及其机制。结果表明，非诺贝特可抑制高糖诱导的系膜细胞外基质Ⅳ型胶原表达上调，抑制细胞进入S期。这种G1期阻滞和ECM抑制是由细胞外信号调节激酶1/2（ERK 1/2）和AKT的磷酸化和激活减少引起的。相反，PPARα siRNA通过激活ERK 1/2和AKT而加速高糖诱导的细胞周期进程。总之，非诺贝特通过抑制PI 3 K/AKT和ERK 1/2信号通路改善葡萄糖诱导的系膜细胞增殖和基质产生。这些机制可能有助于使用非诺贝特治疗糖尿病肾病的良好效果。
Excess mesangial extracellular matrix (ECM) and mesangial cell proliferation is the major pathologic feature of diabetic nephropathy (DN). Fenofibrate, a PPARα agonist, has been shown to attenuate extracellular matrix formation in diabetic nephropathy. However, the mechanisms underlying this effect remain to be elucidated. In this study, the effect of fenofibrate on high-glucose induced cell proliferation and extracellular matrix exertion and its mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, flow cytometry and western blot. The results showed that treatment of mesangial cells (MCs) with fenofibrate repressed high-glucose induced up-regulation of extracellular matrix Collagen-IV, and inhibited entry of cell cycle into the S phase. This G1 arrest and ECM inhibition was caused by the reduction of phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT. On the contrary, PPARα siRNA accelerated high glucose-induced cell cycle progression by ERK1/2 and AKT activation. Taken together, fenofibrate ameliorated glucose-induced mesangial cell proliferation and matrix production via its inhibition of PI3K/AKT and ERK1/2 signaling pathways. Such mechanisms may contribute to the favorable effects of treatment using fenofibrate in diabetic nephropathy.
登录
查看更多内容
影响因子：
5
作者：
Lee, Jung-Jin;Yu, Ji-Yeon;Yun, Yeo-Pyo
通讯作者：
Yun, Yeo-Pyo
DOI：
10.1152/ajprenal.2000.278.4.f667
发表时间：
2000-04-01
影响因子：
4.2
作者：
Portilla, D;Dai, GH;Proia, AD
通讯作者：
Proia, AD
影响因子：
7.7
作者：
Park, CW;Kim, HW;Breyer, MD
通讯作者：
Breyer, MD
DOI：
10.2741/s135
发表时间：
2011-01-01
期刊：
Frontiers in bioscience (Scholar edition)
影响因子：
--
作者：
Heljic, Mediha;Brazil, Derek P
通讯作者：
Brazil, Derek P
影响因子：
5.4
作者：
Ohashi, Naro;Urushihara, Maki;Satou, Ryousuke;Kobori, Hiroyuki
通讯作者：
Kobori, Hiroyuki