Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms
Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms
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汉黄芩素通过 Smad3 依赖性机制对抗肾小管上皮细胞纤维化作用。
DOI：
10.1016/j.ejphar.2016.07.014
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发表时间：
2016-10-15
影响因子：
5
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Meng, Xiao-Ming;Ren, Gui-Ling;Li, Jun
肾纤维化是终末期肾病的常见特征和主要原因，目前尚缺乏有效的治疗方法。在本研究中，我们检测并比较了黄芩的两个主要成分汉黄藤素和汉黄酮苷在转化生长因子-β1处理的人和小鼠肾小管上皮细胞中的抗纤维化作用。结果一致表明，与汉黄连皂苷相比，汉黄连甲素能更有效地抑制转化生长因子-β1诱导的肾小管上皮细胞I型胶原和α-SMA基因和蛋白水平的上调，免疫荧光结果进一步证实，汉黄连甲素能降低转化生长因子-β1诱导的肾小管上皮细胞I型胶原和α-SMA阳性细胞百分率。从机制上讲，汉黄素主要抑制Smad3的磷酸化，但对非典型的转化生长因子-β信号通路如p38和Eric MAP Kinase的作用不明显。此外，在缺乏转化生长因子-β信号或Smad3下游的细胞中，结果表明，即使高浓度的汉黄连甲素也不能进一步降低I型胶原和α-SMA的水平，这表明转化生长因子-β/Smad3信号通路的抑制在汉黄素对转化生长因子-β1刺激的肾小管上皮细胞的治疗作用中起着重要作用。综上所述，我们的结果表明汉黄素可能作为一种潜在的抗纤维化中药单体用于治疗肾纤维化。(C)2016爱思唯尔B.V.保留所有权利。
Renal fibrosis, a common feature and leading cause for End Stage Renal Disease, still lacks effective therapy. In the current study, we detected and compared the anti-fibrotic effects of wogonin and wogonoside, two major components of Scutellaria baicalensis Georgi, in TGF-beta 1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-beta 1-induced upregulated mRNA and protein levels of collagen I and alpha-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and alpha-SMA positive cells in TGF-beta 1-treated tubular epithelial cells. Mechan-istically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-beta signaling pathways, such as p38 and ERIC MAP Kinase. Furthermore, in the cells deficient for TGF-beta signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and alpha-SMA, indicating the essential role of TGF-beta/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-beta 1-stimulated tubular epithelial cells. Collectively, our results indicated that wogonin may be utilized as a potential anti-fibrotic Traditional Chinese Medicine monomer in the treatment of renal fibrosis. (C) 2016 Elsevier B.V. All rights reserved.