Role for alpha3 integrin in EMT and pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive (myo)fibroblast accumulation and collagen deposition. One possible source of (myo)fibroblasts is epithelial cells that undergo epithelial-mesenchymal transition (EMT), a process frequently mediated by TGF-beta. In this issue of the JCI, Kim et al. report that epithelial cell-specific deletion of alpha3 integrin prevents EMT in mice, thereby protecting against bleomycin-induced fibrosis (see the related article beginning on page 213). The authors propose a novel mechanism linking TGF-beta and beta-catenin signaling in EMT through integrin-dependent association of tyrosine-phosphorylated beta-catenin and pSmad2 and suggest targeted disruption of this interaction as a potential therapeutic approach.
Borok
Zea
Z
Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA. zborok@usc.edu
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D001761:Bleomycin / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D039422:Integrin alpha3; D051153:Wnt Proteins; D051176:beta Catenin; D001761:Bleomycin