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NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation
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نویسنده
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Li Wei ,Zheng Nai-Zhong ,Yuan Qi ,Xu Ke ,Yang Fan ,Gu Lei ,Zheng Gu-Yan ,Luo Guo-Jie ,Fan Chun ,Ji Guang-Ju ,Zhang Bo ,Cao Huiqing ,Tian Xiao-Li
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منبع
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journal of molecular medicine - 2016 - دوره : 94 - شماره : 9 - صفحه:993 -1002
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چکیده
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Entry of calcium into cardiomyocyte via l-type calcium channel (ltcc) is fundamental to cardiac contraction. cacna1c, a type of ltcc and a hallmark of a matured ventricular myocyte, is developmentally regulated. here, we identified 138 potential transcription factors by a comparative genomic study on 5-kb promoter regions of cacna1c gene across eight vertebrate species, and showed that six factors were developmentally regulated with the expression of cacna1c in mouse p19cl6 in vitro cardiomyocyte differentiation model. we further demonstrated that the nuclear factor of activated t cells 5 (nfat5) bound to a consensus sequence tggaagcgttc and activated the transcription of cacna1c. the sirna-mediated knockdown of nfat5 suppressed the expression of cacna1c and decreased l-type calcium current in mouse neonatal cardiomyocytes. furthermore, morpholino-mediated knockdown of nfat5 in zebrafish prohibited the expression of cacna1c and resulted in a non-contractile ventricle, while over-expression of either cacna1c or nfat5 rescued this impaired phenotype. thus, nfat5-mediated expression of cacna1c is evolutionarily conserved and critical for cardiac electrophysiological development and maturation of cardiomyocyte.
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کلیدواژه
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L-type calcium channel ,NFAT5 ,Cardiac development ,Comparative genomic ,Transcriptional factor
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آدرس
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Peking University, Department of Human Population Genetics, China, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Peking University, China, Chinese Academy of Sciences, National Laboratory of Biomacromolecules, China, Peking University, Department of Human Population Genetics, China, Peking University, Department of Human Population Genetics, China, Chinese Academy of Sciences, National Laboratory of Biomacromolecules, China, Peking University, Department of Human Population Genetics, China, Peking University, China, The Cleveland Clinic, Department of Biomedical Engineering, USA, Chinese Academy of Sciences, National Laboratory of Biomacromolecules, China, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, Peking University, China, Peking University, Department of Human Population Genetics, China, Peking University, Department of Human Population Genetics, China
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Authors
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