title: Kidney tubular β-catenin signaling controls interstitial fibroblast fate via epithelial-mesenchymal communication.
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.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Tan
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Li
authors.forename: Youhua
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002450:Cell Communication; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D004848:Epithelium / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D058628:Myofibroblasts / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D051176:beta Catenin; D020783:Matrix Metalloproteinase 7