Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms

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• 作者：Xiao-Ming Meng^a ; ^b ; ^c ; ¹ ; Gui-Ling Ren^a ; ¹ ; Li Gao^a ; Hai-Di Li^a ; Wei-Feng Wu^a ; Xiao-Feng Li^a ; ^b ; Tao Xu^a ; ^b ; Xue-Fu Wang^a ; Tao-Tao Ma^a ; Zeng Li^a ; Cheng Huang^a ; ^b ; Yan Huang^a ; ^b ; Lei Zhang^a ; ^b ; Xiong-Wen Lv^a ; ^b ; Jun Li^a ; ^b ; ^{lj@ahmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Renal fibrosis ; TGF-β1 ; Smad3 ; Wogonin
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：789
• 期：Complete
• 页码：134-143
• 全文大小：5249 K

文摘

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-β1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-β1-induced upregulated mRNA and protein levels of collagen I and α-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and α-SMA positive cells in TGF-β1-treated tubular epithelial cells. Mechanistically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-β signaling pathways, such as p38 and ERK MAP Kinase. Furthermore, in the cells deficient for TGF-β signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and α-SMA, indicating the essential role of TGF-β/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-β1-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.