Kidney tubular β-catenin signaling controls interstitial fibroblast fate via epithelial-mesenchymal communication

Sci Rep. 2013;3:1878. doi: 10.1038/srep01878.

Abstract

Activation of β-catenin, the principal mediator of canonical Wnt signaling, is a common pathologic finding in a wide variety of chronic kidney diseases (CKD). While β-catenin is induced predominantly in renal tubular epithelium in CKD, surprisingly, depletion of tubular β-catenin had little effect on the severity of renal fibrosis. Interestingly, less apoptosis was detected in interstitial fibroblasts in knockout mice, which was accompanied by a decreased expression of Bax and Fas ligand (FasL). Tubule-specific knockout of β-catenin diminished renal induction of matrix metalloproteinase (MMP-7), which induced FasL expression in interstitial fibroblasts and potentiated fibroblast apoptosis in vitro. These results demonstrate that loss of tubular β-catenin resulted in enhanced interstitial fibroblast survival due to decreased MMP-7 expression. Our studies uncover a novel role of the tubular β-catenin/MMP-7 axis in controlling the fate of interstitial fibroblasts via epithelial-mesenchymal communication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Communication*
  • Cell Line
  • Cell Survival / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelium / metabolism*
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Fibroblasts / metabolism*
  • Fibrosis
  • Gene Expression Regulation
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Tubules / metabolism*
  • Matrix Metalloproteinase 7 / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Myofibroblasts / metabolism
  • Organ Specificity / genetics
  • Rats
  • Signal Transduction*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Fas Ligand Protein
  • beta Catenin
  • Matrix Metalloproteinase 7