Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma
العنوان: | Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma |
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المؤلفون: | Ju Fang, Jie Yang, Peng-Cheng Cai, Fei Liu, Qian Zhang, Peter A. Greer, Yunchao Su, Huan-Zhong Shi, Yu Zeng, Shan-Shan Rao, Wan-Li Ma, Qing Mu, Lin-Jie Song, Li-Ling Zhou, Hong Ye, Feng‐Zhi Li, Yu Xia, Yu‐Xiu Lin |
المصدر: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 47(2) |
سنة النشر: | 2015 |
مصطلحات موضوعية: | 0301 basic medicine, Immunology, Myocytes, Smooth Muscle, Inflammation, Mechanistic Target of Rapamycin Complex 2, Biology, mTORC2, Collagen Type I, 03 medical and health sciences, Mice, 0302 clinical medicine, medicine, Immunology and Allergy, Animals, Phosphorylation, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Mice, Knockout, Akt/PKB signaling pathway, Calpain, Muscle, Smooth, Dipeptides, Asthma, respiratory tract diseases, 3. Good health, Cell biology, Disease Models, Animal, 030104 developmental biology, Rapamycin-Insensitive Companion of mTOR Protein, 030220 oncology & carcinogenesis, Asthmatic Airway Remodeling, Knockout mouse, biology.protein, Airway Remodeling, Cytokines, medicine.symptom, Proto-Oncogene Proteins c-akt, Signal Transduction |
الوصف: | Background Allergic asthma is characterized by inflammation and airway remodeling. Airway remodeling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in airway smooth muscle remodeling remains unknown. Objective To investigate the role of calpain in asthmatic airway remodeling as well as the underling mechanism. Methods The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analyzed. Results Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodeling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis and cell proliferation of ASMCs, and attenuated airway smooth muscle remodeling in mouse asthma models. Conclusions Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signaling pathway, thereby regulating airway smooth muscle remodeling in asthma. This article is protected by copyright. All rights reserved. |
تدمد: | 1365-2222 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a222544b7ee31d8e0cc2125f98075c5 https://pubmed.ncbi.nlm.nih.gov/27649066 |
حقوق: | CLOSED |
رقم الأكسشن: | edsair.doi.dedup.....8a222544b7ee31d8e0cc2125f98075c5 |
قاعدة البيانات: | OpenAIRE |
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