Isorhynchophylline exerts anti-asthma effects in mice by inhibiting the proliferation of airway smooth muscle cells: The involvement of miR-200a-mediated FOXC1/NF-κB pathway |
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| Institution: | 1. Department of Respiratory Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;2. Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China;3. Department of Emergency Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;1. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;2. College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou, China;3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;1. Department of Respiration, Tianjin First Central Hospital, Tianjin, China;2. Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin, China;1. Clinic of Pulmonary Medicine, University Hospital Basel, Basel, Switzerland;2. Respiratory Cell Research, Department of Biomedicine, University of Basel, Basel, Switzerland;3. Laboratory of Pharmacology, Department of Medicine, Aristotle University of Thessaloniki, Greece;4. Institute of Pathology, University Hospital Basel, Switzerland;1. Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120, China;2. Department of Geratology, the Second People?s Hospital of Shenzhen, Shenzhen 518000, China;1. Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province 510120, China;2. Department of Respiratory Medicine, Xili People’s Hospital, Shenzhen, Guangdong Province 518055, China |
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| Abstract: | Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway. |
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| Keywords: | Airway smooth muscle cells Asthma Isorhynchophylline miR-200a FOXC1 |
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