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Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism
Expression of the nerve growth factor NGF is increased in pulmonary hypertension (PH). We have here studied whether oxidative stress and inflammation, two pathological conditions associated with transforming growth factor-β1 (TGF-β1) in PH, may trigger NGF secretion by pulmonary arterial (PA) cells....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496672/ https://www.ncbi.nlm.nih.gov/pubmed/36139373 http://dx.doi.org/10.3390/cells11182795 |
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author | Bouchet, Clément Cardouat, Guillaume Douard, Matthieu Coste, Florence Robillard, Paul Delcambre, Frédéric Ducret, Thomas Quignard, Jean-François Vacher, Pierre Baudrimont, Isabelle Marthan, Roger Berger, Patrick Guibert, Christelle Freund-Michel, Véronique |
author_facet | Bouchet, Clément Cardouat, Guillaume Douard, Matthieu Coste, Florence Robillard, Paul Delcambre, Frédéric Ducret, Thomas Quignard, Jean-François Vacher, Pierre Baudrimont, Isabelle Marthan, Roger Berger, Patrick Guibert, Christelle Freund-Michel, Véronique |
author_sort | Bouchet, Clément |
collection | PubMed |
description | Expression of the nerve growth factor NGF is increased in pulmonary hypertension (PH). We have here studied whether oxidative stress and inflammation, two pathological conditions associated with transforming growth factor-β1 (TGF-β1) in PH, may trigger NGF secretion by pulmonary arterial (PA) cells. Effects of hydrogen peroxide (H(2)O(2)) and interleukin-1β (IL-1β) were investigated ex vivo on rat pulmonary arteries, as well as in vitro on human PA smooth muscle (hPASMC) or endothelial cells (hPAEC). TβRI expression was assessed by Western blotting. NGF PA secretion was assessed by ELISA after TGF-β1 blockade (anti-TGF-β1 siRNA, TGF-β1 blocking antibodies, TβRI kinase, p38 or Smad3 inhibitors). TβRI PA expression was evidenced by Western blotting both ex vivo and in vitro. H(2)O(2) or IL-1β significantly increased NGF secretion by hPASMC and hPAEC, and this effect was significantly reduced when blocking TGF-β1 expression, binding to TβRI, TβRI activity, or signaling pathways. In conclusion, oxidative stress and inflammation may trigger TGF-β1 secretion by hPASMC and hPAEC. TGF-β1 may then act as an autocrine factor on these cells, increasing NGF secretion via TβRI activation. Since NGF and TGF-β1 are relevant growth factors involved in PA remodeling, such mechanisms may therefore be relevant to PH pathophysiology. |
format | Online Article Text |
id | pubmed-9496672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94966722022-09-23 Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism Bouchet, Clément Cardouat, Guillaume Douard, Matthieu Coste, Florence Robillard, Paul Delcambre, Frédéric Ducret, Thomas Quignard, Jean-François Vacher, Pierre Baudrimont, Isabelle Marthan, Roger Berger, Patrick Guibert, Christelle Freund-Michel, Véronique Cells Article Expression of the nerve growth factor NGF is increased in pulmonary hypertension (PH). We have here studied whether oxidative stress and inflammation, two pathological conditions associated with transforming growth factor-β1 (TGF-β1) in PH, may trigger NGF secretion by pulmonary arterial (PA) cells. Effects of hydrogen peroxide (H(2)O(2)) and interleukin-1β (IL-1β) were investigated ex vivo on rat pulmonary arteries, as well as in vitro on human PA smooth muscle (hPASMC) or endothelial cells (hPAEC). TβRI expression was assessed by Western blotting. NGF PA secretion was assessed by ELISA after TGF-β1 blockade (anti-TGF-β1 siRNA, TGF-β1 blocking antibodies, TβRI kinase, p38 or Smad3 inhibitors). TβRI PA expression was evidenced by Western blotting both ex vivo and in vitro. H(2)O(2) or IL-1β significantly increased NGF secretion by hPASMC and hPAEC, and this effect was significantly reduced when blocking TGF-β1 expression, binding to TβRI, TβRI activity, or signaling pathways. In conclusion, oxidative stress and inflammation may trigger TGF-β1 secretion by hPASMC and hPAEC. TGF-β1 may then act as an autocrine factor on these cells, increasing NGF secretion via TβRI activation. Since NGF and TGF-β1 are relevant growth factors involved in PA remodeling, such mechanisms may therefore be relevant to PH pathophysiology. MDPI 2022-09-07 /pmc/articles/PMC9496672/ /pubmed/36139373 http://dx.doi.org/10.3390/cells11182795 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 Bouchet, Clément Cardouat, Guillaume Douard, Matthieu Coste, Florence Robillard, Paul Delcambre, Frédéric Ducret, Thomas Quignard, Jean-François Vacher, Pierre Baudrimont, Isabelle Marthan, Roger Berger, Patrick Guibert, Christelle Freund-Michel, Véronique Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title | Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title_full | Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title_fullStr | Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title_full_unstemmed | Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title_short | Inflammation and Oxidative Stress Induce NGF Secretion by Pulmonary Arterial Cells through a TGF-β1-Dependent Mechanism |
title_sort | inflammation and oxidative stress induce ngf secretion by pulmonary arterial cells through a tgf-β1-dependent mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496672/ https://www.ncbi.nlm.nih.gov/pubmed/36139373 http://dx.doi.org/10.3390/cells11182795 |
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