title: miR-7a/b attenuates post-myocardial infarction remodeling and protects H9c2 cardiomyoblast against hypoxia-induced apoptosis involving Sp1 and PARP-1.
abstract: miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to investigate the function of miR-7a/b in post-MI remodeling in a mouse model and to determine the underlying mechanisms involved. miR-7a/b overexpression improved cardiac function, attenuated cardiac remodeling and reduced fibrosis and apoptosis, whereas miR-7a/b silencing caused the opposite effects. Furthermore, miR-7a/b overexpression suppressed specific protein 1 (Sp1) and poly (ADP-ribose) polymerase (PARP-1) expression both in vivo and in vitro, and a luciferase reporter activity assay showed that miR-7a/b could directly bind to Sp1. Mithramycin, an inhibitor of the DNA binding activity of Sp1, effectively repressed PARP-1 and caspase-3, whereas knocking down miR-7a/b partially counteracted these beneficial effects. Additionally, an immunoprecipitation assay indicated that hypoxia triggered activation of the binding activity of Sp1 to the promoters of PARP-1 and caspase-3, which is abrogated by miR-7a/b. In summary, these findings identified miR-7a/b as protectors of cardiac remodeling and hypoxia-induced injury in H9c2 cardiomyoblasts involving Sp1 and PARP-1.
authors.affiliation: Department of Health Care, China-Japan Friendship Hospital, Ministry of Health, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Geng
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiao-Teng
authors.initials: XT
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Xing
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Xia
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Liang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D064752:Atrial Remodeling / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D008926:Plicamycin / Q000008:administration & dosage; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D000071137:Poly (ADP-Ribose) Polymerase-1; D053148:Caspase 3; D008926:Plicamycin