RGD Reference Report - Clusterin attenuates the development of renal fibrosis. - Rat Genome Database

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Clusterin attenuates the development of renal fibrosis.

Authors: Jung, GS  Kim, MK  Jung, YA  Kim, HS  Park, IS  Min, BH  Lee, KU  Kim, JG  Park, KG  Lee, IK 
Citation: Jung GS, etal., J Am Soc Nephrol. 2012 Jan;23(1):73-85. doi: 10.1681/ASN.2011010048. Epub 2011 Nov 3.
RGD ID: 9068421
Pubmed: PMID:22052058   (View Abstract at PubMed)
PMCID: PMC3269926   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2011010048   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal fibrosis  ISOClu (Rattus norvegicus) and Clu (Mus musculus)9068421associated with Ureteral ObstructionRGD 
renal fibrosis  IMP 9068421; 9068421associated with Ureteral ObstructionRGD 
renal fibrosis  ISOFn1 (Mus musculus)9068421; 9068421protein:increased expression:kidney:RGD 
renal fibrosis  IEP 9068421protein:increased expression:kidney:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Clu  (clusterin)
Fn1  (fibronectin 1)

Genes (Mus musculus)
Clu  (clusterin)
Fn1  (fibronectin 1)

Genes (Homo sapiens)
CLU  (clusterin)
FN1  (fibronectin 1)


Additional Information