Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition
Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition
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DOI：
10.1254/jphs.14173fp
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发表时间：
2014-12-01
影响因子：
3.5
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Zhou, Xiangjun;Zhang, Jie;Wang, Wei
肾纤维化的主要特征是间质成纤维细胞的活化和增殖以及细胞外基质（ECM）组分（包括纤连蛋白（FN）和胶原）的过度合成和积累。本研究探讨姜黄素对肾间质成纤维细胞增殖的影响及其机制。在单侧输尿管梗阻（UUO）小鼠中，通过天狼星红和免疫组织化学染色观察ECM组分，并通过蛋白质印迹分析进行定量。增殖细胞核抗原和α-平滑肌肌动蛋白（α-SMA）的双重染色，以及MTT和流式细胞术测定，以测量成纤维细胞增殖。通过蛋白质印迹法评估磷酸化Smad 2/3（p-Smad 2/3）和过氧化物酶体增殖物激活受体-γ（PPAR-gamma）的蛋白质表达。姜黄素治疗减少了UUO动物肾脏中I型胶原和FN的积累。TGF-β 1诱导大鼠肾间质成纤维细胞（NRK-49 F）活化。姜黄素处理抑制成纤维细胞增殖，细胞周期被阻滞在G1期。姜黄素处理上调PPAR-gamma的表达，下调p-Smad 2/3的表达。这些结果表明，姜黄素治疗通过减少由PPAR-gamma和Smad依赖性TGF-β 1信号传导介导的成纤维细胞增殖和ECM积累来改善肾纤维化。
Renal fibrosis is mainly characterized by activation and proliferation of interstitial fibroblasts and by excessive synthesis and accumulation of extracellular matrix (ECM) components, including fibronectin (FN) and collagen. This study investigated the effects of curcumin on proliferation of renal interstitial fibroblasts and their underlying mechanisms in vivo and in vitro. ECM components were visualized by Sirius red and immunohistochemistry staining and quantified by western blot analysis in mice with unilateral ureteral obstruction (UUO). Duplex staining for proliferating cell nuclear antigen and a-smooth muscle actin (alpha-SMA), as well as MTT and flow cytometry assays, were performed to measure fibroblast proliferation. Protein expression of phosphorylated Smad2/3 (p-Smad2/3) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) were assessed by western blotting. Curcumin treatment decreased the accumulation of type I collagen and FN in the kidney of animals with UUO. Activation of rat renal interstitial fibroblasts (NRK-49F) was induced by TGF-beta 1. Curcumin treatment inhibited fibroblast proliferation and the cell cycle was arrested in the G1 phase. Curcumin treatment upregulated the expression of PPAR-gamma and downregulated the expression of p-Smad2/3. These results suggest that curcumin treatment ameliorates renal fibrosis by reducing fibroblast proliferation and ECM accumulation mediated by PPAR-gamma and Smad-dependent TGF-beta 1 signaling.