Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Laurino, Annunziatina, Spinelli, Valentina, Gencarelli, Manuela, Balducci, Valentina, Dini, Leonardo, Diolaiuti, Lorenzo, Ghionzoli, Marco, Messineo, Antonio, Mugelli, Alessandro, Cerbai, Elisabetta, Raimondi, Laura, Sartiani, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783460583201308672
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
work_keys_str_mv AT laurinoannunziatina angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT spinellivalentina angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT gencarellimanuela angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT balduccivalentina angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT dinileonardo angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT diolaiutilorenzo angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT ghionzolimarco angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT messineoantonio angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT mugellialessandro angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT cerbaielisabetta angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT raimondilaura angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways
AT sartianilaura angiotensiniidriveshumansatellitecellstowardhypertrophyandmyofibroblasttransdifferentiationbytwoindependentpathways