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Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension

Endothelin-1 (ET-1) is a vasoactive and profibrotic peptide that plays a pivotal role in diseases such as systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), by inducing fibrosis and vascular remodeling. Such effects may be sustained by the induction of aldosterone production and rea...

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Autores principales: Argentino, Giuseppe, Barbieri, Alessandro, Beri, Ruggero, Bason, Caterina, Ruzzenente, Andrea, Olivieri, Oliviero, Tinazzi, Elisa, Puccetti, Antonio, Vitali, Claudio, Del Papa, Nicoletta, Friso, Simonetta, Lunardi, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687242/
https://www.ncbi.nlm.nih.gov/pubmed/36359285
http://dx.doi.org/10.3390/biomedicines10112765
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author Argentino, Giuseppe
Barbieri, Alessandro
Beri, Ruggero
Bason, Caterina
Ruzzenente, Andrea
Olivieri, Oliviero
Tinazzi, Elisa
Puccetti, Antonio
Vitali, Claudio
Del Papa, Nicoletta
Friso, Simonetta
Lunardi, Claudio
author_facet Argentino, Giuseppe
Barbieri, Alessandro
Beri, Ruggero
Bason, Caterina
Ruzzenente, Andrea
Olivieri, Oliviero
Tinazzi, Elisa
Puccetti, Antonio
Vitali, Claudio
Del Papa, Nicoletta
Friso, Simonetta
Lunardi, Claudio
author_sort Argentino, Giuseppe
collection PubMed
description Endothelin-1 (ET-1) is a vasoactive and profibrotic peptide that plays a pivotal role in diseases such as systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), by inducing fibrosis and vascular remodeling. Such effects may be sustained by the induction of aldosterone production and reactive oxygen species (ROS). We have used fibroblasts obtained from skin of healthy donors and SSc patients and commercial fibroblasts from lung to evaluate whether ET-1 is able to stimulate ROS production directly or indirectly through aldosterone induction. We found that ET-1 receptors are present in all types of fibroblasts analyzed, whereas the expression of mineralocorticoid receptor (MCR) is lower in dermal fibroblasts from healthy donors (HDFs) compared to fibroblasts derived from lung (HPFs) or from skin of SSc patients (SScHDFs). ET-1 induces ROS production in HDFs and SScHDFs after 24 h of incubation involving its receptor B (ETB), whereas aldosterone exerts its effects after 40 min of incubation. Moreover, ROS production was inhibited by the pre-incubation of cells with MCR inhibitor. Our results indicate that ET-1 induces ROS indirectly through aldosterone production suggesting that aldosterone may play a pivotal role in the pathogenesis of SSc and PAH.
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spelling pubmed-96872422022-11-25 Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension Argentino, Giuseppe Barbieri, Alessandro Beri, Ruggero Bason, Caterina Ruzzenente, Andrea Olivieri, Oliviero Tinazzi, Elisa Puccetti, Antonio Vitali, Claudio Del Papa, Nicoletta Friso, Simonetta Lunardi, Claudio Biomedicines Article Endothelin-1 (ET-1) is a vasoactive and profibrotic peptide that plays a pivotal role in diseases such as systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), by inducing fibrosis and vascular remodeling. Such effects may be sustained by the induction of aldosterone production and reactive oxygen species (ROS). We have used fibroblasts obtained from skin of healthy donors and SSc patients and commercial fibroblasts from lung to evaluate whether ET-1 is able to stimulate ROS production directly or indirectly through aldosterone induction. We found that ET-1 receptors are present in all types of fibroblasts analyzed, whereas the expression of mineralocorticoid receptor (MCR) is lower in dermal fibroblasts from healthy donors (HDFs) compared to fibroblasts derived from lung (HPFs) or from skin of SSc patients (SScHDFs). ET-1 induces ROS production in HDFs and SScHDFs after 24 h of incubation involving its receptor B (ETB), whereas aldosterone exerts its effects after 40 min of incubation. Moreover, ROS production was inhibited by the pre-incubation of cells with MCR inhibitor. Our results indicate that ET-1 induces ROS indirectly through aldosterone production suggesting that aldosterone may play a pivotal role in the pathogenesis of SSc and PAH. MDPI 2022-10-31 /pmc/articles/PMC9687242/ /pubmed/36359285 http://dx.doi.org/10.3390/biomedicines10112765 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Argentino, Giuseppe
Barbieri, Alessandro
Beri, Ruggero
Bason, Caterina
Ruzzenente, Andrea
Olivieri, Oliviero
Tinazzi, Elisa
Puccetti, Antonio
Vitali, Claudio
Del Papa, Nicoletta
Friso, Simonetta
Lunardi, Claudio
Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title_full Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title_fullStr Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title_full_unstemmed Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title_short Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
title_sort profibrotic effects of endothelin-1 on fibroblasts are mediated by aldosterone in vitro: relevance to the pathogenesis and therapy of systemic sclerosis and pulmonary arterial hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687242/
https://www.ncbi.nlm.nih.gov/pubmed/36359285
http://dx.doi.org/10.3390/biomedicines10112765
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