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
Source PublicationJOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume26Issue:8Pages:1827-1838
AbstractTGF-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.
DOI10.1681/ASN.2014040363
Indexed BySCI
Language英语
WOS IDWOS:000358895100012
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/25083
Collection植物化学与西部植物资源持续利用国家重点实验室
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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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