A role for Wnt-4 in renal fibrosis

Am J Physiol Renal Physiol. 2002 Mar;282(3):F431-41. doi: 10.1152/ajprenal.0009.2001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Cytosol / metabolism
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / transplantation
  • Fibrosis
  • Gene Expression / physiology
  • Kidney Diseases, Cystic / metabolism
  • Kidney Diseases, Cystic / pathology
  • Kidney Tubules, Collecting / metabolism
  • Kidney Tubules, Collecting / pathology
  • Mice
  • Mice, Mutant Strains
  • Nephritis, Interstitial / metabolism*
  • Nephritis, Interstitial / pathology*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / analysis
  • Trans-Activators*
  • Wnt Proteins
  • Wnt4 Protein
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Trans-Activators
  • Wnt Proteins
  • Wnt4 Protein
  • Wnt4 protein, mouse
  • beta Catenin