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The Orphan Nuclear Receptor SHP Attenuates Renal Fibrosis

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Author(s)
Gwon-Soo JungMi-Kyung KimMi Sun ChoeKyeong-Min LeeHye-Soon KimYoung Joo ParkHueng-Sik ChoiKi-Up LeeKeun-Gyu ParkIn-Kyu Lee
Keimyung Author(s)
Kim, Mi KyungKim, Hye SoonPark, Keun GyuChoe, Mi Sun
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Journal Title
Journal of the American Society of Nephrology
Issued Date
2009
Volume
20
Issue
10
Abstract
The accumulation of extracellular matrix proteins is a common feature of fibrotic kidney diseases. Accumulating evidence suggests that TGF-β and plasminogen activator inhibitor type 1 (PAI-1) promote the development of renal fibrosis by stimulating the generation and inhibiting the removal of matrix proteins. The small heterodimer partner (SHP) represses PAI-1 expression in the liver by inhibiting TGF-β signaling, but whether SHP inhibits renal fibrosis is unknown. Here, unilateral ureteral obstruction (UUO) markedly increased the expression of PAI-1, type I collagen, and fibronectin but decreased SHP gene expression. Moreover, in kidneys of SHP−/− mice, the expression of PAI-1, type I collagen, fibronectin and α-smooth muscle actin (α-SMA) were higher compared with those in kidneys of wild-type mice. In addition, loss of SHP accelerated renal fibrosis after UUO. Adenovirus-mediated overexpression of SHP in cultured rat mesangial cells and renal tubular epithelial cells inhibited TGF-β-stimulated expression of PAI-1, type I collagen, and fibronectin. SHP inhibited TGF-β- and Smad3-stimulated PAI-1 promoter activities as well as TGF-β-stimulated binding of Smad3 to its consensus response element on the PAI-1 promoter. Similarly, in vivo, adenovirus-mediated overexpression of SHP in the kidney inhibited the expression of UUO-induced PAI-1, type I collagen, fibronectin, and α-SMA. In summary, SHP attenuates renal fibrosis in obstructive nephropathy, making its pathway a possible therapeutic target for chronic kidney disease.
Keimyung Author(s)(Kor)
김미경
김혜순
박근규
최미선
Publisher
School of Medicine
Citation
Gwon-Soo Jung et al. (2009). The Orphan Nuclear Receptor SHP Attenuates Renal Fibrosis. Journal of the American Society of Nephrology, 20(10), 2162–2170. doi: 10.1681/ASN.2008121232
Type
Article
ISSN
1046-6673
DOI
10.1681/ASN.2008121232
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34265
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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