VEGF/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis

التفاصيل البيبلوغرافية
العنوان: VEGF/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis
المؤلفون: Li-Mei Liang, Meng Wang, Hong Ye, Xiaorong Wang, Wan-Li Ma, Jian-Bao Xin, Pei-Pei Cheng, Fan Yu, Li Xiong, Liang Xiong, Lin-Jie Song, Xin-Liang He, Yu-Zhi Lu
المصدر: American Journal of Physiology-Lung Cellular and Molecular Physiology. 320:L990-L1004
بيانات النشر: American Physiological Society, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Vascular Endothelial Growth Factor A, 0301 basic medicine, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Physiology, Cell, Epithelium, Permeability, Bleomycin, 03 medical and health sciences, Basal (phylogenetics), Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Physiology (medical), Pulmonary fibrosis, medicine, Animals, Humans, Distribution (pharmacology), Lung, business.industry, Cell Biology, respiratory system, medicine.disease, Idiopathic Pulmonary Fibrosis, Rats, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Permeability (electromagnetism), Pleura, business, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src
الوصف: The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. 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’s 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.
تدمد: 1522-1504
1040-0605
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::632437aa1ada7691fa25f58f811708f4
https://doi.org/10.1152/ajplung.00436.2020
رقم الأكسشن: edsair.doi.dedup.....632437aa1ada7691fa25f58f811708f4
قاعدة البيانات: OpenAIRE