EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture

Abstract We found that the coagulation and cytokine pathways were important mechanisms involve in the degeneration of intervertebral discs (IVD) using a microarray approach to analyze gene expression in different grades of specimens. Furthermore, using a cytokine/chemokine array, a significant incre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bor-Ren Huang, Tzu-Sheng Chen, Da-Tian Bau, I-Chen Chuang, Cheng-Fang Tsai, Pei-Chun Chang, Dah-Yuu Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e0108c8e41e4316b9f0ccb94c3cc01a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8e0108c8e41e4316b9f0ccb94c3cc01a
record_format	dspace
spelling	oai:doaj.org-article:8e0108c8e41e4316b9f0ccb94c3cc01a2021-12-02T12:32:04ZEGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture10.1038/s41598-017-09122-32045-2322https://doaj.org/article/8e0108c8e41e4316b9f0ccb94c3cc01a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09122-3https://doaj.org/toc/2045-2322Abstract We found that the coagulation and cytokine pathways were important mechanisms involve in the degeneration of intervertebral discs (IVD) using a microarray approach to analyze gene expression in different grades of specimens. Furthermore, using a cytokine/chemokine array, a significant increase in CXCL8 expression was observed in human nucleus pulposus (NP) cells after thrombin treatment. The enhancement of CXCL8 expression by thrombin was activated by the PAR1 receptor. Importantly, analysis of degenerated human NP tissue samples showed that EGFR expression positively correlated with the grade of tissue degeneration. In NP cells, thrombin caused an increase in phosphorylation of the EGFR at the Tyr1068, and treatment with the pharmacological EGFR inhibitor, AG1473 effectively blocked thrombin-enhanced CXCL8 production. Surprisingly, inhibition of STAT3 for 24 h decreased expression of EGFR. Treatment with thrombin also increased Akt and GSK3α/β activation; this activation was also blocked by EGFR inhibitor. Although c-Src, ERK, and FAK were activated by thrombin, only c-Src and ERK were involved in the STAT3/CXCL8 induction. Our findings indicate that stimulation of an inflammatory response in NP cells by thrombin is part of a specific pathophysiology that modulates the EGFR activation through activation of Src/ERK/STAT3 signaling.Bor-Ren HuangTzu-Sheng ChenDa-Tian BauI-Chen ChuangCheng-Fang TsaiPei-Chun ChangDah-Yuu LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bor-Ren Huang Tzu-Sheng Chen Da-Tian Bau I-Chen Chuang Cheng-Fang Tsai Pei-Chun Chang Dah-Yuu Lu EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
description	Abstract We found that the coagulation and cytokine pathways were important mechanisms involve in the degeneration of intervertebral discs (IVD) using a microarray approach to analyze gene expression in different grades of specimens. Furthermore, using a cytokine/chemokine array, a significant increase in CXCL8 expression was observed in human nucleus pulposus (NP) cells after thrombin treatment. The enhancement of CXCL8 expression by thrombin was activated by the PAR1 receptor. Importantly, analysis of degenerated human NP tissue samples showed that EGFR expression positively correlated with the grade of tissue degeneration. In NP cells, thrombin caused an increase in phosphorylation of the EGFR at the Tyr1068, and treatment with the pharmacological EGFR inhibitor, AG1473 effectively blocked thrombin-enhanced CXCL8 production. Surprisingly, inhibition of STAT3 for 24 h decreased expression of EGFR. Treatment with thrombin also increased Akt and GSK3α/β activation; this activation was also blocked by EGFR inhibitor. Although c-Src, ERK, and FAK were activated by thrombin, only c-Src and ERK were involved in the STAT3/CXCL8 induction. Our findings indicate that stimulation of an inflammatory response in NP cells by thrombin is part of a specific pathophysiology that modulates the EGFR activation through activation of Src/ERK/STAT3 signaling.
format	article
author	Bor-Ren Huang Tzu-Sheng Chen Da-Tian Bau I-Chen Chuang Cheng-Fang Tsai Pei-Chun Chang Dah-Yuu Lu
author_facet	Bor-Ren Huang Tzu-Sheng Chen Da-Tian Bau I-Chen Chuang Cheng-Fang Tsai Pei-Chun Chang Dah-Yuu Lu
author_sort	Bor-Ren Huang
title	EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
title_short	EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
title_full	EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
title_fullStr	EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
title_full_unstemmed	EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
title_sort	egfr is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8e0108c8e41e4316b9f0ccb94c3cc01a
work_keys_str_mv	AT borrenhuang egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT tzushengchen egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT datianbau egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT ichenchuang egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT chengfangtsai egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT peichunchang egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture AT dahyuulu egfrisapivotalregulatorofthrombinmediatedinflammationinprimaryhumannucleuspulposusculture
_version_	1718394171060912128

EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture

Ejemplares similares