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MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling

AIMS: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remo...

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Autores principales: Li, Guoqi, Shao, Yihui, Guo, Hong Chang, Zhi, Ying, Qiao, Bokang, Ma, Ke, Du, Jie, Lai, Yong Qiang, Li, Yulin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302889/
https://www.ncbi.nlm.nih.gov/pubmed/34358309
http://dx.doi.org/10.1093/cvr/cvab248
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author Li, Guoqi
Shao, Yihui
Guo, Hong Chang
Zhi, Ying
Qiao, Bokang
Ma, Ke
Du, Jie
Lai, Yong Qiang
Li, Yulin
author_facet Li, Guoqi
Shao, Yihui
Guo, Hong Chang
Zhi, Ying
Qiao, Bokang
Ma, Ke
Du, Jie
Lai, Yong Qiang
Li, Yulin
author_sort Li, Guoqi
collection PubMed
description AIMS: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling. METHODS AND RESULTS: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/β. CONCLUSIONS: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.
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spelling pubmed-93028892022-07-22 MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling Li, Guoqi Shao, Yihui Guo, Hong Chang Zhi, Ying Qiao, Bokang Ma, Ke Du, Jie Lai, Yong Qiang Li, Yulin Cardiovasc Res Original Article AIMS: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling. METHODS AND RESULTS: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/β. CONCLUSIONS: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting. Oxford University Press 2021-08-06 /pmc/articles/PMC9302889/ /pubmed/34358309 http://dx.doi.org/10.1093/cvr/cvab248 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Li, Guoqi
Shao, Yihui
Guo, Hong Chang
Zhi, Ying
Qiao, Bokang
Ma, Ke
Du, Jie
Lai, Yong Qiang
Li, Yulin
MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title_full MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title_fullStr MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title_full_unstemmed MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title_short MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
title_sort microrna-27b-3p down-regulates fgf1 and aggravates pathological cardiac remodelling
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302889/
https://www.ncbi.nlm.nih.gov/pubmed/34358309
http://dx.doi.org/10.1093/cvr/cvab248
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