EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2

Objective: Growth factors [transforming growth factor-β (TGF-β), epidermal growth factor (EGF), endothelin-1 (ET-1)] stimulate proteoglycan synthesis resulting in retention and accumulation of low density lipoprotein (LDL) in vessel intima and leading to atherosclerosis development. This study inves...

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Auteurs principaux:	Hossein Babaahmadi-Rezaei, Alireza Kheirollah, Mojtaba Rashidi, Faezeh Seif, Zahra Niknam, Masoumeh Zamanpour
Format:	article
Langue:	EN
Publié:	Royan Institute (ACECR), Tehran 2021
Sujets:	chsy1 enzyme endothelin-1 epidermal growth factor nadph oxidase Medicine R Science Q
Accès en ligne:	https://doaj.org/article/572497b1833d43bf9a026bca93e31231
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spelling	oai:doaj.org-article:572497b1833d43bf9a026bca93e312312021-11-07T07:01:47ZEGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/210.22074/cellj.2021.73922228-58062228-5814https://doaj.org/article/572497b1833d43bf9a026bca93e312312021-10-01T00:00:00Zhttps://celljournal.org/journal/article/fulltext/egf-receptor-transactivation-by-endothelin-1-increased-chsy-1-protein-mediated-by-nadph-oxidase-and-phosphorylation-of-erk12.pdfhttps://doaj.org/toc/2228-5806https://doaj.org/toc/2228-5814Objective: Growth factors [transforming growth factor-β (TGF-β), epidermal growth factor (EGF), endothelin-1 (ET-1)] stimulate proteoglycan synthesis resulting in retention and accumulation of low density lipoprotein (LDL) in vessel intima and leading to atherosclerosis development. This study investigated the role of ET-1 on the expression of CHSY1, proteoglycan synthesizing enzyme, through both EGF and TGF-β receptor transactivation in human vascular smooth muscle cells (VSMCs). Also, we explored the involvement of NADPH oxidase (NOX), an important intermediate of redox signaling, in ET-1 transactivated EGF receptor (EGFR) through endothelin receptors. Materials and Methods: In this experimental study, phosphorylated ERK1/2 and CHSY1 protein levels in the human VSMCs were measured by Western blot analysis using anti phospho-ERK1/2 (Thr202/Tyr204) and anti CHSY1 antibodies. Results: ET-1 (100 nM) and EGF (100 ng/ml) stimulated ERK1/2 phosphorylation and inhibited in the presence of bosentan (ET receptor inhibitor), AG1478 (EGFR inhibitor), and DPI (NOX antagonist). Also, ET-1 treatment increased CHSY1 enzyme level; this response was suppressed by bosentan, AG1478, DPI, and SB431542, TGF-β receptor antagonist. This study revealed that ET-1 increases expression of CHSY1 through transactivation of EGF and TGF-β receptors. Conclusion: Transactivation through the EGF receptor mediated by phospho-ERK1/2 leads to expression of CHSY1 protein. EGF receptor transactivation by ET-1 is shown for the first time, to be dependent on NOX enzymes.Hossein Babaahmadi-RezaeiAlireza KheirollahMojtaba RashidiFaezeh SeifZahra NiknamMasoumeh ZamanpourRoyan Institute (ACECR), Tehranarticlechsy1 enzymeendothelin-1epidermal growth factornadph oxidaseMedicineRScienceQENCell Journal, Vol 23, Iss 5, Pp 510-515 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chsy1 enzyme endothelin-1 epidermal growth factor nadph oxidase Medicine R Science Q
spellingShingle	chsy1 enzyme endothelin-1 epidermal growth factor nadph oxidase Medicine R Science Q Hossein Babaahmadi-Rezaei Alireza Kheirollah Mojtaba Rashidi Faezeh Seif Zahra Niknam Masoumeh Zamanpour EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
description	Objective: Growth factors [transforming growth factor-β (TGF-β), epidermal growth factor (EGF), endothelin-1 (ET-1)] stimulate proteoglycan synthesis resulting in retention and accumulation of low density lipoprotein (LDL) in vessel intima and leading to atherosclerosis development. This study investigated the role of ET-1 on the expression of CHSY1, proteoglycan synthesizing enzyme, through both EGF and TGF-β receptor transactivation in human vascular smooth muscle cells (VSMCs). Also, we explored the involvement of NADPH oxidase (NOX), an important intermediate of redox signaling, in ET-1 transactivated EGF receptor (EGFR) through endothelin receptors. Materials and Methods: In this experimental study, phosphorylated ERK1/2 and CHSY1 protein levels in the human VSMCs were measured by Western blot analysis using anti phospho-ERK1/2 (Thr202/Tyr204) and anti CHSY1 antibodies. Results: ET-1 (100 nM) and EGF (100 ng/ml) stimulated ERK1/2 phosphorylation and inhibited in the presence of bosentan (ET receptor inhibitor), AG1478 (EGFR inhibitor), and DPI (NOX antagonist). Also, ET-1 treatment increased CHSY1 enzyme level; this response was suppressed by bosentan, AG1478, DPI, and SB431542, TGF-β receptor antagonist. This study revealed that ET-1 increases expression of CHSY1 through transactivation of EGF and TGF-β receptors. Conclusion: Transactivation through the EGF receptor mediated by phospho-ERK1/2 leads to expression of CHSY1 protein. EGF receptor transactivation by ET-1 is shown for the first time, to be dependent on NOX enzymes.
format	article
author	Hossein Babaahmadi-Rezaei Alireza Kheirollah Mojtaba Rashidi Faezeh Seif Zahra Niknam Masoumeh Zamanpour
author_facet	Hossein Babaahmadi-Rezaei Alireza Kheirollah Mojtaba Rashidi Faezeh Seif Zahra Niknam Masoumeh Zamanpour
author_sort	Hossein Babaahmadi-Rezaei
title	EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
title_short	EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
title_full	EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
title_fullStr	EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
title_full_unstemmed	EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2
title_sort	egf receptor transactivation by endothelin-1 increased chsy-1 mediated by nadph oxidase and phosphorylation of erk1/2
publisher	Royan Institute (ACECR), Tehran
publishDate	2021
url	https://doaj.org/article/572497b1833d43bf9a026bca93e31231
work_keys_str_mv	AT hosseinbabaahmadirezaei egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12 AT alirezakheirollah egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12 AT mojtabarashidi egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12 AT faezehseif egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12 AT zahraniknam egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12 AT masoumehzamanpour egfreceptortransactivationbyendothelin1increasedchsy1mediatedbynadphoxidaseandphosphorylationoferk12
_version_	1718443546439057408

EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2

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