COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis

Abstract COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. I...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaojie Peng, Jianzhong Li, Siwei Tan, Minyi Xu, Jin Tao, Jie Jiang, Huiling Liu, Bin Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d89ca8c8f04e470d989ae71604490efb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d89ca8c8f04e470d989ae71604490efb
record_format	dspace
spelling	oai:doaj.org-article:d89ca8c8f04e470d989ae71604490efb2021-12-02T16:07:45ZCOX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis10.1038/s41598-017-01169-62045-2322https://doaj.org/article/d89ca8c8f04e470d989ae71604490efb2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01169-6https://doaj.org/toc/2045-2322Abstract COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following DSS-induced injury, β-arr1 deficient mice showed increased signs of colitis compared to β-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in β-arr1 deficient mice. In parallel, HCT116 cells transfected with β-arr1 siRNA were examined in the presence or absence of PGE2 in vitro. PGE2 treatment in the β-arr1 WT/KO DSS model and β-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated β-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates the β-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE2 in UC.Xiaojie PengJianzhong LiSiwei TanMinyi XuJin TaoJie JiangHuiling LiuBin WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaojie Peng Jianzhong Li Siwei Tan Minyi Xu Jin Tao Jie Jiang Huiling Liu Bin Wu COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
description	Abstract COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following DSS-induced injury, β-arr1 deficient mice showed increased signs of colitis compared to β-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in β-arr1 deficient mice. In parallel, HCT116 cells transfected with β-arr1 siRNA were examined in the presence or absence of PGE2 in vitro. PGE2 treatment in the β-arr1 WT/KO DSS model and β-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated β-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates the β-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE2 in UC.
format	article
author	Xiaojie Peng Jianzhong Li Siwei Tan Minyi Xu Jin Tao Jie Jiang Huiling Liu Bin Wu
author_facet	Xiaojie Peng Jianzhong Li Siwei Tan Minyi Xu Jin Tao Jie Jiang Huiling Liu Bin Wu
author_sort	Xiaojie Peng
title	COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
title_short	COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
title_full	COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
title_fullStr	COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
title_full_unstemmed	COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
title_sort	cox-1/pge2/ep4 alleviates mucosal injury by upregulating β-arr1-mediated akt signaling in colitis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d89ca8c8f04e470d989ae71604490efb
work_keys_str_mv	AT xiaojiepeng cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT jianzhongli cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT siweitan cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT minyixu cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT jintao cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT jiejiang cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT huilingliu cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis AT binwu cox1pge2ep4alleviatesmucosalinjurybyupregulatingbarr1mediatedaktsignalingincolitis
_version_	1718384748837994496

COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis

Ejemplares similares