| First Author | Jung GS | Year | 2012 |
| Journal | J Am Soc Nephrol | Volume | 23 |
| Issue | 1 | Pages | 73-85 |
| PubMed ID | 22052058 | Mgi Jnum | J:228569 |
| Mgi Id | MGI:5707929 | Doi | 10.1681/ASN.2011010048 |
| Citation | Jung GS, et al. (2012) Clusterin attenuates the development of renal fibrosis. J Am Soc Nephrol 23(1):73-85 |
| abstractText | 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-beta-stimulated PAI-1, type I collagen, and fibronectin. Clusterin inhibited TGF-beta-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. |
