title: Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR.
abstract: β-adrenergic receptors (β-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mg·kg(-1)·d(-1) for 7 days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB) is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.
authors.affiliation: Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 71006, China.|Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.|Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 71006, China.
authors.forename: Xiaopu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.|Key laboratory of Chinese internal medicine of MOE and Beijing, Dongzhimen hospital, Beijing university of Chinese medicine, 5# Haiyuncang lane, Dongcheng district, Beijing100700, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007545:Isoproterenol; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol