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Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson\u2019s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF\/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF\/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF\/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF\/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.<\/jats:p>","DOI":"10.1152\/ajplung.00436.2020","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T08:00:45Z","timestamp":1617177645000},"page":"L990-L1004","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["VEGF\/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis"],"prefix":"10.1152","volume":"320","author":[{"given":"Yu-Zhi","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People\u2019s Republic of 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