Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Am Soc Nephrol. 2012 Jan;23(1):73-85. doi: 10.1681/ASN.2011010048. Epub 2011 Nov 3.

Clusterin attenuates the development of renal fibrosis.

Author information

  • 1Department of Internal Medicine, Kyungpook National University School of Medicine, 50 Samdeok-2ga, Jung-gu, Daegu 700-721, South Korea.

Erratum in

  • J Am Soc Nephrol. 2012 Jun;23(6):1125.

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.

PMID:
22052058
[PubMed - indexed for MEDLINE]
PMCID:
PMC3269926
Free PMC Article

Images from this publication.See all images (9)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
Figure 9.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk