c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs

Abstract The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jinnan Xiang, Yiqun Zhang, Dandan Bao, Na Cao, Xin Zhang, Ping Li, Shoutao Qiu, Jigang Guo, Dan He, Baojie Li, Liqing Yao, Huijuan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ef9cd61f8ffb4cf0936115d01b4c0c06
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ef9cd61f8ffb4cf0936115d01b4c0c06
record_format	dspace
spelling	oai:doaj.org-article:ef9cd61f8ffb4cf0936115d01b4c0c062021-12-02T15:05:58Zc-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs10.1038/s41598-017-03569-02045-2322https://doaj.org/article/ef9cd61f8ffb4cf0936115d01b4c0c062017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03569-0https://doaj.org/toc/2045-2322Abstract The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl −/− mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.Jinnan XiangYiqun ZhangDandan BaoNa CaoXin ZhangPing LiShoutao QiuJigang GuoDan HeBaojie LiLiqing YaoHuijuan LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jinnan Xiang Yiqun Zhang Dandan Bao Na Cao Xin Zhang Ping Li Shoutao Qiu Jigang Guo Dan He Baojie Li Liqing Yao Huijuan Liu c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
description	Abstract The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl −/− mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.
format	article
author	Jinnan Xiang Yiqun Zhang Dandan Bao Na Cao Xin Zhang Ping Li Shoutao Qiu Jigang Guo Dan He Baojie Li Liqing Yao Huijuan Liu
author_facet	Jinnan Xiang Yiqun Zhang Dandan Bao Na Cao Xin Zhang Ping Li Shoutao Qiu Jigang Guo Dan He Baojie Li Liqing Yao Huijuan Liu
author_sort	Jinnan Xiang
title	c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
title_short	c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
title_full	c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
title_fullStr	c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
title_full_unstemmed	c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
title_sort	c-abl regulates gastrointestinal muscularis propria homeostasis via erks
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ef9cd61f8ffb4cf0936115d01b4c0c06
work_keys_str_mv	AT jinnanxiang cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT yiqunzhang cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT dandanbao cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT nacao cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT xinzhang cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT pingli cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT shoutaoqiu cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT jigangguo cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT danhe cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT baojieli cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT liqingyao cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks AT huijuanliu cablregulatesgastrointestinalmuscularispropriahomeostasisviaerks
_version_	1718388679802617856

c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs

Ejemplares similares