title: Interaction of Src and Alpha-V Integrin Regulates Fibroblast Migration and Modulates Lung Fibrosis in A Preclinical Model of Lung Fibrosis.
abstract: Src kinase is known to regulate fibroblast migration. However, the contribution of integrin and Src kinase interaction to lung fibrosis has not been mechanistically investigated. Our data demonstrate that integrin alpha v (αV) recruited Src kinase and that leads to subsequent Src activation in fibroblasts plated on fibrotic matrix, osteopontin. Src interaction with integrin αV is required for integrin αV-mediated Src activation, and the subsequent fibroblast migration. The study identified that β5 and β3 are the major integrins for this effect on osteopontin. In contrast, integrins β1, β6, and β8 did not have a critical role in this phenomenon. Importantly, Src inhibitor significantly reduces fibroblast migration stimulated by PDGF-BB and reduced in vivo lung fibrosis in mice. Src inhibitor reduced Src activation and blocked the signaling transduction by integrin αV, inhibited migration signaling pathways and reduced extracellular matrix protein production, and blocked myofibroblast differentiation in vivo in mouse lung tissues. The present study supports that the interaction of Src Kinase and integrins plays a critical role in the development of lung fibrosis and the signaling involved may present a novel opportunity to target deadly fibrotic diseases.
authors.affiliation: Comprehensive Liver Cancer Center, 302 hospital, Beijing, China.
authors.forename: Yin-Ying
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, the Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, China.|Department of Medicine, Pulmonary Division, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.affiliation: Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, PLA General Hospital, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Geriatric Hematology, PLA General Hospital, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhai
authors.affiliation: Research Center for Medical Sciences, The Third Xiang-Ya Hospital and the Department of Laboratory Animals, Xiang-Ya School of Medicine, Central South University, Hunan, China.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Gao
authors.affiliation: Department of Medicine, Pulmonary Division, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D039564:Integrin alphaV / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D053495:Osteopontin / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D039564:Integrin alphaV; D053495:Osteopontin; D019061:src-Family Kinases