Let-7a Is an Antihypertrophic Regulator in the Heart via Targeting Calmodulin

Autor: Xin Zhou, Guiye Zhang, You Shu, Ti Yang, Ming Gao, Wei Zhao, Shenjian Luo, Yanan Zhuang, Renzhong Lu, Fei Sun, Wei Mu, Yanjie Lu, Chaoqian Xu, Fengzhi Ding
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
calmodulin
medicine.medical_specialty
Cardiomegaly
Real-Time Polymerase Chain Reaction
Applied Microbiology and Biotechnology
Muscle hypertrophy
03 medical and health sciences
angiotensin Ⅱ
Downregulation and upregulation
Western blot
Calmodulin
In vivo
Internal medicine
Natriuretic Peptide
Brain
medicine
Myocyte
Animals
Myocytes
Cardiac
RNA
Messenger
Molecular Biology
3' Untranslated Regions
Ecology
Evolution
Behavior and Systematics
Cells
Cultured
miRNA
Reporter gene
let-7a
medicine.diagnostic_test
business.industry
Angiotensin II
Cell Biology
Rats
Cardiac hypertrophy
MicroRNAs
030104 developmental biology
Real-time polymerase chain reaction
Endocrinology
cardiovascular system
business
hormones
hormone substitutes
and hormone antagonists
Atrial Natriuretic Factor
Developmental Biology
Research Paper
Zdroj: International Journal of Biological Sciences
ISSN: 1449-2288
Popis: Background: MicroRNAs (miRNAs) have been emerged as important regulator in a multiple of cardiovascular disease, including arrhythmia, cardiac hypertrophy and fibrosis, and myocardial infarction. The aim of this study was to investigate whether miRNA let-7a has antihypertrophic effects in angiotensin II (AngII)-induced cardiac hypertrophy. Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to AngII for 36 h as a cellular model of hypertrophy; subcutaneous injection of AngII for 2 weeks was used to establish a mouse model of cardiac hypertrophy in vivo study. Cell surface area (CSA) was measured by immunofluorescence cytochemistry; expression of hypertrophy-related genes ANP, BNP, β-MHC was detected by Real-time PCR; luciferase activity assay was performed to confirm the miRNA's binding site in the calmodulin (CaM) gene; CaM protein was detected by Western blot; the hypertrophy parameters were measured by echocardiographic assessment. Results: The expression of let-7a was decreased in AngII-induced cardiac hypertrophy in vitro and in vivo. Overexpression of let-7a attenuated AngII-induced increase of cell surface area and repressed the increased mRNA levels of ANP, BNP and β-MHC. Dual-luciferase reporter assay showed that let-7a could bind to the 3'UTR of CaM 1 gene. Let-7a downregulated the expression of CaM protein. In vivo, let-7a produced inhibitory effects on cardiac hypertrophy, including the downregulation of cross-sectional area of cardiomyocytes in mouse heart, the reduction of IVSD and LVPWD, the suppression of hypertrophy marker genes ANP, BNP, β-MHC mRNA level, and the downregulation of CaM protein level. Conclusions: let-7a possesses a prominent anti-hypertrophic property by targeting CaM genes. The findings provide new insight into molecular mechanism of cardiac hypertrophy.
Databáze: OpenAIRE
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