title: Cadherin-11 contributes to pulmonary fibrosis: potential role in TGF-β production and epithelial to mesenchymal transition.
abstract: Pulmonary fibrosis, characterized by excess deposition of extracellular matrix by myofibroblasts, is a serious component of chronic lung diseases. Cadherin-11 (CDH11) is increased in wound healing and fibrotic skin. We hypothesized that CDH11 is increased in pulmonary fibrosis and contributes its development. CDH11 expression was assessed in lung tissue from idiopathic pulmonary fibrosis patients. The role of CDH11 in lung fibrosis was determined using the bleomycin model of pulmonary fibrosis, and in vitro analyses were performed on A549 cells during the process of epithelial to mesenchymal transition (EMT). Immunohistochemical studies demonstrated CDH11 expression on fibroblasts, epithelial cells, and alveolar macrophages of patients with pulmonary fibrosis and mice given bleomycin. Interestingly, CDH11-deficient mice had decreased fibrotic endpoints in the bleomycin model of pulmonary fibrosis compared to wild-type mice. Furthermore, anti-CDH11-neutralizing monoclonal antibodies successfully treated established pulmonary fibrosis induced by bleomycin. TGF-β levels were reduced in bronchoalveolar lavage (BAL) fluid, BAL cells, and primary alveolar macrophages from CDH11-deficient mice. Mechanistic studies demonstrated that TGF-β up-regulated CDH11 expression on A549 cells, and inhibition of CDH11 expression using siRNA reduced TGF-β-induced EMT. Together, these results identify CDH11 as a novel therapeutic target for pulmonary fibrosis.
authors: Department of Biochemistry and Molecular Biology, Pediatric Research Center, University of Texas Health Science Center, Houston, Texas, USA.
authors: Daniel J
authors: DJ
authors: Schneider
authors: Minghua
authors: M
authors: Wu
authors: Thuy T
authors: TT
authors: Le
authors: Seo-Hee
authors: SH
authors: Cho
authors: Michael B
authors: MB
authors: Brenner
authors: Michael R
authors: MR
authors: Blackburn
authors: Sandeep K
authors: SK
authors: Agarwal
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D015820:Cadherins; D016212:Transforming Growth Factor beta; D001761:Bleomycin; C086960:osteoblast cadherin