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Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways
Skeletal muscle regeneration is ensured by satellite cells (SC), which upon activation undergo self-renewal and myogenesis. The correct sequence of healing events may be offset by inflammatory and/or fibrotic factors able to promote fibrosis and consequent muscle wasting. Angiotensin-II (Ang) is an...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801484/ https://www.ncbi.nlm.nih.gov/pubmed/31623362 http://dx.doi.org/10.3390/ijms20194912 |
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author | Laurino, Annunziatina Spinelli, Valentina Gencarelli, Manuela Balducci, Valentina Dini, Leonardo Diolaiuti, Lorenzo Ghionzoli, Marco Messineo, Antonio Mugelli, Alessandro Cerbai, Elisabetta Raimondi, Laura Sartiani, Laura |
author_facet | Laurino, Annunziatina Spinelli, Valentina Gencarelli, Manuela Balducci, Valentina Dini, Leonardo Diolaiuti, Lorenzo Ghionzoli, Marco Messineo, Antonio Mugelli, Alessandro Cerbai, Elisabetta Raimondi, Laura Sartiani, Laura |
author_sort | Laurino, Annunziatina |
collection | PubMed |
description | Skeletal muscle regeneration is ensured by satellite cells (SC), which upon activation undergo self-renewal and myogenesis. The correct sequence of healing events may be offset by inflammatory and/or fibrotic factors able to promote fibrosis and consequent muscle wasting. Angiotensin-II (Ang) is an effector peptide of the renin angiotensin system (RAS), of which the direct role in human SCs (hSCs) is still controversial. Based on the hypertrophic and fibrogenic effects of Ang via transient receptor potential canonical (TRPC) channels in cardiac and renal tissues, we hypothesized a similar axis in hSCs. Toward this aim, we demonstrated that hSCs respond to acute Ang stimulation, dose-dependently enhancing p-mTOR, p-AKT, p-ERK1/2 and p-P38. Additionally, sub-acute Ang conditioning increased cell size and promoted trans-differentiation into myofibroblasts. To provide a mechanistic hypothesis on TRPC channel involvement in the processes, we proved that TRPC channels mediate a basal calcium entry into hSCs that is stimulated by acute Ang and strongly amplified by sub-chronic Ang conditioning. Altogether, these findings demonstrate that Ang induces a fate shift of hSCs into myofibroblasts and provide a basis to support a benefit of RAS and TRPC channel blockade to oppose muscle fibrosis. |
format | Online Article Text |
id | pubmed-6801484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68014842019-10-31 Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways Laurino, Annunziatina Spinelli, Valentina Gencarelli, Manuela Balducci, Valentina Dini, Leonardo Diolaiuti, Lorenzo Ghionzoli, Marco Messineo, Antonio Mugelli, Alessandro Cerbai, Elisabetta Raimondi, Laura Sartiani, Laura Int J Mol Sci Article Skeletal muscle regeneration is ensured by satellite cells (SC), which upon activation undergo self-renewal and myogenesis. The correct sequence of healing events may be offset by inflammatory and/or fibrotic factors able to promote fibrosis and consequent muscle wasting. Angiotensin-II (Ang) is an effector peptide of the renin angiotensin system (RAS), of which the direct role in human SCs (hSCs) is still controversial. Based on the hypertrophic and fibrogenic effects of Ang via transient receptor potential canonical (TRPC) channels in cardiac and renal tissues, we hypothesized a similar axis in hSCs. Toward this aim, we demonstrated that hSCs respond to acute Ang stimulation, dose-dependently enhancing p-mTOR, p-AKT, p-ERK1/2 and p-P38. Additionally, sub-acute Ang conditioning increased cell size and promoted trans-differentiation into myofibroblasts. To provide a mechanistic hypothesis on TRPC channel involvement in the processes, we proved that TRPC channels mediate a basal calcium entry into hSCs that is stimulated by acute Ang and strongly amplified by sub-chronic Ang conditioning. Altogether, these findings demonstrate that Ang induces a fate shift of hSCs into myofibroblasts and provide a basis to support a benefit of RAS and TRPC channel blockade to oppose muscle fibrosis. MDPI 2019-10-03 /pmc/articles/PMC6801484/ /pubmed/31623362 http://dx.doi.org/10.3390/ijms20194912 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Laurino, Annunziatina Spinelli, Valentina Gencarelli, Manuela Balducci, Valentina Dini, Leonardo Diolaiuti, Lorenzo Ghionzoli, Marco Messineo, Antonio Mugelli, Alessandro Cerbai, Elisabetta Raimondi, Laura Sartiani, Laura Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title | Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title_full | Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title_fullStr | Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title_full_unstemmed | Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title_short | Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways |
title_sort | angiotensin-ii drives human satellite cells toward hypertrophy and myofibroblast trans-differentiation by two independent pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801484/ https://www.ncbi.nlm.nih.gov/pubmed/31623362 http://dx.doi.org/10.3390/ijms20194912 |
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