MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway

Abstract Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGFβ signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic ther...

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Autores principales:	Fatemeh Yousefi, Bahram M. Soltani, Shahram Rabbani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6257983b5d44a14995870fc1e4b96c1
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spelling	oai:doaj.org-article:d6257983b5d44a14995870fc1e4b96c12021-12-02T14:16:17ZMicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway10.1038/s41598-021-82226-z2045-2322https://doaj.org/article/d6257983b5d44a14995870fc1e4b96c12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82226-zhttps://doaj.org/toc/2045-2322Abstract Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGFβ signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic therapy. The relationship between ncRNAs and TGFβ signaling pathway has been extensively studied. Here, we have provided several lines of evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGFβ signaling. First, bioinformatics analysis and dual luciferase assay validated a direct interaction between the miR-331 and TGFβ-R1 3′UTR sequence which results in the downregulation of TGFβ signaling pathway. Second, miR-331 expression was inversely related to the expression of a number of genes which are involved in extracellular matrix (ECM) production and deposition processes, both in the in vivo and in vitro fibrosis models. Third, in cultured mouse and human cardiac myofibroblasts (CMyoFbs) under ISO treatment, overexpression of miR-331 decreased the expression level of fibrosis-related genes. Consistently, western blot analysis confirmed that miR-331 overexpression ended in both Smad3 and Col1A1 protein level reduction in mouse cardiac myofibroblasts. Finally, flow cytometry analysis, cyclin D1 and D2 gene expression analysis, and wound-healing assay confirmed the inhibitory effect of miR-331 against cell proliferation and migration in ISO-treated cardiac myofibroblasts. Taken together, accumulative results showed that miR-331 reduced the level of fibrosis-related proteins in cardiac myofibroblasts culture via regulating TGFβ signaling pathway.Fatemeh YousefiBahram M. SoltaniShahram RabbaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fatemeh Yousefi Bahram M. Soltani Shahram Rabbani MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
description	Abstract Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGFβ signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic therapy. The relationship between ncRNAs and TGFβ signaling pathway has been extensively studied. Here, we have provided several lines of evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGFβ signaling. First, bioinformatics analysis and dual luciferase assay validated a direct interaction between the miR-331 and TGFβ-R1 3′UTR sequence which results in the downregulation of TGFβ signaling pathway. Second, miR-331 expression was inversely related to the expression of a number of genes which are involved in extracellular matrix (ECM) production and deposition processes, both in the in vivo and in vitro fibrosis models. Third, in cultured mouse and human cardiac myofibroblasts (CMyoFbs) under ISO treatment, overexpression of miR-331 decreased the expression level of fibrosis-related genes. Consistently, western blot analysis confirmed that miR-331 overexpression ended in both Smad3 and Col1A1 protein level reduction in mouse cardiac myofibroblasts. Finally, flow cytometry analysis, cyclin D1 and D2 gene expression analysis, and wound-healing assay confirmed the inhibitory effect of miR-331 against cell proliferation and migration in ISO-treated cardiac myofibroblasts. Taken together, accumulative results showed that miR-331 reduced the level of fibrosis-related proteins in cardiac myofibroblasts culture via regulating TGFβ signaling pathway.
format	article
author	Fatemeh Yousefi Bahram M. Soltani Shahram Rabbani
author_facet	Fatemeh Yousefi Bahram M. Soltani Shahram Rabbani
author_sort	Fatemeh Yousefi
title	MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
title_short	MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
title_full	MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
title_fullStr	MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
title_full_unstemmed	MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway
title_sort	microrna‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the tgfβ/smad3 signaling pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d6257983b5d44a14995870fc1e4b96c1
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MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway

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