Clusterin attenuates the development of renal fibrosis

Gwon Soo Jung, Mi Kyung Kim, Yun A. Jung, Hye Soon Kim, In Sun Park, Bon Hong Min, Ki Up Lee, Jung Guk Kim, Keun Gyu Park, In Kyu Lee

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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. Comparedwithwild-typemice, clusterin-deficientmice 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.

Original languageEnglish
Pages (from-to)73-85
Number of pages13
JournalJournal of the American Society of Nephrology
Volume23
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

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ASJC Scopus subject areas

  • Nephrology

Cite this

Jung, G. S., Kim, M. K., Jung, Y. A., Kim, H. S., Park, I. S., Min, B. H., Lee, K. U., Kim, J. G., Park, K. G., & Lee, I. K. (2012). Clusterin attenuates the development of renal fibrosis. Journal of the American Society of Nephrology, 23(1), 73-85. https://doi.org/10.1681/ASN.2011010048