ANO1 regulates cardiac fibrosis via ATI-mediated MAPK pathway |
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| Affiliation: | 1. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, People’s Republic of China;2. Department of Physiology, Medical College of Shihezi University, Shihezi, People’s Republic of China;1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;2. Cardiovascular Research Institute of Wuhan University, Wuhan, China;3. Hubei Key Laboratory of Cardiology, Wuhan, China;1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United States;2. Department of Pharmacology & Chemical Biology, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United States;3. Department of Emergency, Union Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, China;1. Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China;2. Department of Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China;1. Transplantation Laboratory, University of Helsinki, Helsinki, Finland;2. Department of Bacteriology and Immunology and Research Programs Unit, University of Helsinki, and HUSLAB, Helsinki, Finland;3. Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;4. National Institute for Health and Welfare, Helsinki, Finland;5. HUH Heart and Lung Center, Division of Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;1. Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, PO Box 17666, United Arab Emirates;2. Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, PO Box 17666, United Arab Emirates;1. College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea;2. Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea |
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| Abstract: | Cardiac fibrosis is associated with most of heart diseases, but its molecular mechanism remains unclear. Anoctamin-1 (ANO1), a calcium-activated chloride channels (CaCCs) protein, plays a critical role in various pathophysiological processes. In the current study, we identified ANO1 expression in myocardial infarction (MI) model of rat and verified the role of ANO1 in cardiac fibrosis using transcriptomics combined with RNAi assays. we found that ANO1 expression was increased during the first two weeks, and decreased in the third week after MI. Fluorescence double labeling showed that ANO1 was mainly expressed in cardiac fibroblasts (CFs) and displayed an increased expression in CFs with proliferation tendency. The proliferation and secretion of CFs were markedly inhibited by knockdown of ANO1. RNA-Seq showed that most of the downregulation genes were related to the proliferation of CFs and cardiac fibrosis. After ANO1 knockdown, the expressions of angiotensin II type 1 receptor (AT1R) and cell nuclear proliferation antigen were markedly reduced, and the phosphorylation levels of MEK and ERK1/2 was decreased significantly, indicating that ANO1 regulate cardiac fibrosis through ATIR-mediated MAPK signaling pathway. These findings would be useful for the development of therapeutic strategies targeting ANO1 to treat and prevent cardiac fibrosis. |
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| Keywords: | ANO1 Calcium-activated chloride channel Cardiac fibroblasts Cardiac fibrosis |
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