title: Clusterin attenuates the development of renal fibrosis.
abstract: Upregulation of clusterin occurs in several renal diseases and models of nephrotoxicity, but whether this promotes injury or is a protective reaction to injury is unknown. Here, in the mouse unilateral ureteral obstruction model, obstruction markedly increased the expression of clusterin, plasminogen activator inhibitor-1 (PAI-1), type I collagen, and fibronectin. Compared with wild-type mice, clusterin-deficient mice exhibited higher levels of PAI-1, type I collagen, and fibronectin and accelerated renal fibrosis in response to obstruction. In cultured rat tubular epithelium-like cells, adenovirus-mediated overexpression of clusterin inhibited the expression of TGF-β-stimulated PAI-1, type I collagen, and fibronectin. Clusterin inhibited TGF-β-stimulated Smad3 activity via inhibition of Smad3 phosphorylation and its nuclear translocation. Moreover, intrarenal delivery of adenovirus-expressing clusterin upregulated expression of clusterin in tubular epithelium-like cells and attenuated obstruction-induced renal fibrosis. In conclusion, clusterin attenuates renal fibrosis in obstructive nephropathy. These results suggest that upregulation of clusterin during renal injury is a protective response against the development of renal fibrosis.
authors: Department of Internal Medicine, Kyungpook National University School of Medicine, 50 Samdeok-2ga, Jung-gu, Daegu 700-721, South Korea.
authors: Gwon-Soo
authors: GS
authors: Jung
authors: Mi-Kyung
authors: MK
authors: Kim
authors: Yun-A
authors: YA
authors: Jung
authors: Hye-Soon
authors: HS
authors: Kim
authors: In-Sun
authors: IS
authors: Park
authors: Bon-Hong
authors: BH
authors: Min
authors: Ki-Up
authors: KU
authors: Lee
authors: Jung-Guk
authors: JG
authors: Kim
authors: Keun-Gyu
authors: KG
authors: Park
authors: In-Kyu
authors: IK
authors: Lee
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051152:Clusterin / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D058258:Serpin E2 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D015820:Cadherins; D051152:Clusterin; D024042:Collagen Type I; D005353:Fibronectins; D058258:Serpin E2; C511869:Serpine2 protein, mouse