| GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-beta-Induced Smad3 Phosphorylation | |
| Ai, Jun; Nie, Jing; He, Jiangbo; Guo, Qin; Li, Mei; Lei, Ying; Liu, Youhua; Zhou, Zhanmei; Zhu, Fengxin; Liang, Min; Cheng, Yongxian; Hou, Fan Fan | |
| 2015-08-01 | |
| 发表期刊 | JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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| 卷号 | 26期号:8页码:1827-1838 |
| 摘要 | TGF-beta 1, via Smad-dependent or Smad-independent signaling, has a central role in the pathogenesis of renal fibrosis. This pathway has been recognized as a potential target for antifibrotic therapy. Here, we identified GQ5, a small molecular phenolic compound isolated from the dried resin of Toxicodendron vernicifluum, as a potent and selective inhibitor of TGF-beta 1-induced Smad3 phosphorylation. In TGF-beta 1-stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF-beta type I receptor (T beta RI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as alpha-smooth muscle actin (alpha-SMA), collagen I, and fibronectin. Notably, intraperitoneal administration of GQ5 in rats immediately after unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation in UUO kidneys, suppressed renal expression of alpha-SMA, collagen I, and fibronectin, and resulted in impressive renal protection after obstructive injury. Late administration of GQ5 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders' renal fibrosis in rats by selective inhibition of TGF-beta 1-induced Smad3 phosphorylation. |
| DOI | 10.1681/ASN.2014040363 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000358895100012 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/25083 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Ai, Jun,Nie, Jing,He, Jiangbo,et al. GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-beta-Induced Smad3 Phosphorylation[J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,2015,26(8):1827-1838. |
| APA | Ai, Jun.,Nie, Jing.,He, Jiangbo.,Guo, Qin.,Li, Mei.,...&Hou, Fan Fan.(2015).GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-beta-Induced Smad3 Phosphorylation.JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,26(8),1827-1838. |
| MLA | Ai, Jun,et al."GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-beta-Induced Smad3 Phosphorylation".JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 26.8(2015):1827-1838. |
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