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Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation

Endothelin‐1 (ET‐1) is implicated in the development of atherosclerosis and mediates glycosaminoglycan (GAG) chain hyperelongation on proteoglycans. Our aim was to identify the ET‐1‐mediated signalling pathway involving NADPH oxidase (NOX), p38 MAP kinsae and Smad2 linker region phosphorylation (pho...

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Autores principales: Babaahmadi‐Rezaei, Hossein, Mohamed, Raafat, Dayati, Parisa, Mehr, Reyhaneh Niayesh, Seif, Faezeh, Sharifat, Narges, Khedri, Azam, Kamato, Danielle, Little, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322435/
https://www.ncbi.nlm.nih.gov/pubmed/35527471
http://dx.doi.org/10.1111/1440-1681.13650
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author Babaahmadi‐Rezaei, Hossein
Mohamed, Raafat
Dayati, Parisa
Mehr, Reyhaneh Niayesh
Seif, Faezeh
Sharifat, Narges
Khedri, Azam
Kamato, Danielle
Little, Peter J.
author_facet Babaahmadi‐Rezaei, Hossein
Mohamed, Raafat
Dayati, Parisa
Mehr, Reyhaneh Niayesh
Seif, Faezeh
Sharifat, Narges
Khedri, Azam
Kamato, Danielle
Little, Peter J.
author_sort Babaahmadi‐Rezaei, Hossein
collection PubMed
description Endothelin‐1 (ET‐1) is implicated in the development of atherosclerosis and mediates glycosaminoglycan (GAG) chain hyperelongation on proteoglycans. Our aim was to identify the ET‐1‐mediated signalling pathway involving NADPH oxidase (NOX), p38 MAP kinsae and Smad2 linker region phosphorylation (phospho‐Smad2L) regulate GAG synthesising enzymes mRNA expression (C4ST‐1 and ChSy1) involved in GAG chains hyperelongation in human vascular smooth muscle cells (VSMCs). Signalling intermediates were detected and quantified by Western blotting and the mRNA levels of GAG synthesising enzymes were assessed by quantitative real‐time polymerase chain reaction (qRT‐PCR). ET‐1 treatment of human VSMCs resulted in an increase in phospho‐Smad2L level. The TGF‐β receptor antagonist, SB431542 and the mixed ET(A) and ET(B) receptor antagonist bosentan, inhibited ET‐1‐mediated phospho‐Smad2L level. In the presence of apocynin and diphenyleneiodonium chloride (DPI) (NOX inhibitors) and SB239063 (p38 inhibitor) ET‐1‐mediated phospho‐Smad2L levels were inhibited. The gene expression levels of GAG synthesising enzymes post‐ET‐1 treatment were increased compared to untreated controls (p < 0.01). The ET‐mediated the mRNA levels of these enzymes were blocked by the bosentan, SB431542, SB239063, DPI, apocynin and antioxidant N‐acetyl‐L‐cysteine (NAC). ET‐1‐mediated signalling to GAG synthesising enzymes gene expression occurs via transactivation‐dependent pathway involving NOX, p38 MAP kinsae and Smad2 linker region phosphorylation.
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spelling pubmed-93224352022-07-30 Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation Babaahmadi‐Rezaei, Hossein Mohamed, Raafat Dayati, Parisa Mehr, Reyhaneh Niayesh Seif, Faezeh Sharifat, Narges Khedri, Azam Kamato, Danielle Little, Peter J. Clin Exp Pharmacol Physiol Original Articles Endothelin‐1 (ET‐1) is implicated in the development of atherosclerosis and mediates glycosaminoglycan (GAG) chain hyperelongation on proteoglycans. Our aim was to identify the ET‐1‐mediated signalling pathway involving NADPH oxidase (NOX), p38 MAP kinsae and Smad2 linker region phosphorylation (phospho‐Smad2L) regulate GAG synthesising enzymes mRNA expression (C4ST‐1 and ChSy1) involved in GAG chains hyperelongation in human vascular smooth muscle cells (VSMCs). Signalling intermediates were detected and quantified by Western blotting and the mRNA levels of GAG synthesising enzymes were assessed by quantitative real‐time polymerase chain reaction (qRT‐PCR). ET‐1 treatment of human VSMCs resulted in an increase in phospho‐Smad2L level. The TGF‐β receptor antagonist, SB431542 and the mixed ET(A) and ET(B) receptor antagonist bosentan, inhibited ET‐1‐mediated phospho‐Smad2L level. In the presence of apocynin and diphenyleneiodonium chloride (DPI) (NOX inhibitors) and SB239063 (p38 inhibitor) ET‐1‐mediated phospho‐Smad2L levels were inhibited. The gene expression levels of GAG synthesising enzymes post‐ET‐1 treatment were increased compared to untreated controls (p < 0.01). The ET‐mediated the mRNA levels of these enzymes were blocked by the bosentan, SB431542, SB239063, DPI, apocynin and antioxidant N‐acetyl‐L‐cysteine (NAC). ET‐1‐mediated signalling to GAG synthesising enzymes gene expression occurs via transactivation‐dependent pathway involving NOX, p38 MAP kinsae and Smad2 linker region phosphorylation. John Wiley and Sons Inc. 2022-05-17 2022-07 /pmc/articles/PMC9322435/ /pubmed/35527471 http://dx.doi.org/10.1111/1440-1681.13650 Text en © 2022 The Authors. Clinical and Experimental Pharmacology and Physiology published by John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Babaahmadi‐Rezaei, Hossein
Mohamed, Raafat
Dayati, Parisa
Mehr, Reyhaneh Niayesh
Seif, Faezeh
Sharifat, Narges
Khedri, Azam
Kamato, Danielle
Little, Peter J.
Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title_full Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title_fullStr Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title_full_unstemmed Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title_short Endothelin‐1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation
title_sort endothelin‐1 dependent expression of gag genes involves nox and p38 mediated smad linker region phosphorylation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322435/
https://www.ncbi.nlm.nih.gov/pubmed/35527471
http://dx.doi.org/10.1111/1440-1681.13650
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