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Publication : A role for Wnt-4 in renal fibrosis.

First Author  Surendran K Year  2002
Journal  Am J Physiol Renal Physiol Volume  282
Issue  3 Pages  F431-41
PubMed ID  11832423 Mgi Jnum  J:75544
Mgi Id  MGI:2177035 Doi  10.1152/ajprenal.0009.2001
Citation  Surendran K, et al. (2002) A role for Wnt-4 in renal fibrosis. Am J Physiol Renal Physiol 282(3):F431-41
abstractText  Wnt-4 is a secreted glycoprotein that is critical for genitourinary development but found only in the most distal collecting duct epithelium in the normal murine adult kidney. Wnt4 expression is induced throughout the collecting ducts in four murine models of renal injury that produce tubulointerstitial fibrosis: folic acid-induced nephropathy, unilateral ureteral obstruction, renal needle puncture, and genetic polycystic kidney disease. Wnt4 activation induced by injury is limited to collecting ducts, with initial activation in the collecting duct epithelium followed by activation in fibrotic lesions surrounding the collecting ducts. The highest cellular Wnt4 expression is in interstitial fibroblasts in the fibrotic lesions that also express high levels of collagen-alpha1(I) mRNA and alpha-smooth muscle actin. In support of a functional role for Wnt-4 in these activated myofibroblasts, Wnt-4 induces stabilization of cytosolic beta-catenin in a cultured myofibroblast cell line. Furthermore, Wnt-4-producing fibroblasts placed under the renal capsule of adult mice induce lesions with tubular epithelial destruction. These observations suggest a role for Wnt-4 in the pathogenesis of renal fibrosis.
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