Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice

Abstract Our previous study indicated that streptozotocin (STZ)‐induced diabetes leads to colonic platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used west...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yu‐Jia Li, Jun‐Ping Ao, Xu Huang, Hong‐Li Lu, Han‐Yue Fu, Ni‐Na Song, Wen‐Xie Xu, Jie Chen
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	colon diabetic mice PAR2 PDGFRα+ cells proliferation Physiology QP1-981
Acceso en línea:	https://doaj.org/article/e425ff118a0645f8b39367ef3322523a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e425ff118a0645f8b39367ef3322523a
record_format	dspace
spelling	oai:doaj.org-article:e425ff118a0645f8b39367ef3322523a2021-11-15T09:54:40ZInvolvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice2051-817X10.14814/phy2.15099https://doaj.org/article/e425ff118a0645f8b39367ef3322523a2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15099https://doaj.org/toc/2051-817XAbstract Our previous study indicated that streptozotocin (STZ)‐induced diabetes leads to colonic platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used western blotting, immunohistochemistry, and quantitative PCR to investigate whether proteinase‐activated receptor 2 (PAR2) mediates PDGFRα+ cell proliferation. Our results showed that PDGFRα, PAR2, and Ki‐67 coexpression was increased in the diabetic colonic muscle layer. PDGFRα and PAR2 mRNA and protein expression levels were also markedly enhanced in the diabetic colonic muscle layer. Mice treated with 2‐furoyl‐LIGRLO‐amide (2‐F‐L‐a), a PAR2 agonist, exhibited significant colon elongation and increased smooth muscle weight. In the 2‐F‐L‐a‐treated mice, PDGFRα, PAR2, and Ki‐67 coexpression was increased and PDGFRα and PAR2 mRNA and protein expression was significantly enhanced in the colonic smooth muscle layer. 2‐F‐L‐a also increased proliferation and PDGFRα expression in NIH/3T3 cells cultured in high glucose, while LY294002, a PI3K antagonist, decreased cell proliferation and PDGFRα expression. PI3K and Akt protein and mRNA expression and p‐Akt protein expression in diabetic and 2‐F‐L‐a‐treated mice were markedly reduced in colonic smooth muscle. 2‐F‐L‐a also reduced PI3K, Akt, and p‐Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα+ cells through the PI3K/Akt signaling pathway in the colon of STZ‐induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes.Yu‐Jia LiJun‐Ping AoXu HuangHong‐Li LuHan‐Yue FuNi‐Na SongWen‐Xie XuJie ChenWileyarticlecolondiabetic micePAR2PDGFRα+ cellsproliferationPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colon diabetic mice PAR2 PDGFRα+ cells proliferation Physiology QP1-981
spellingShingle	colon diabetic mice PAR2 PDGFRα+ cells proliferation Physiology QP1-981 Yu‐Jia Li Jun‐Ping Ao Xu Huang Hong‐Li Lu Han‐Yue Fu Ni‐Na Song Wen‐Xie Xu Jie Chen Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
description	Abstract Our previous study indicated that streptozotocin (STZ)‐induced diabetes leads to colonic platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used western blotting, immunohistochemistry, and quantitative PCR to investigate whether proteinase‐activated receptor 2 (PAR2) mediates PDGFRα+ cell proliferation. Our results showed that PDGFRα, PAR2, and Ki‐67 coexpression was increased in the diabetic colonic muscle layer. PDGFRα and PAR2 mRNA and protein expression levels were also markedly enhanced in the diabetic colonic muscle layer. Mice treated with 2‐furoyl‐LIGRLO‐amide (2‐F‐L‐a), a PAR2 agonist, exhibited significant colon elongation and increased smooth muscle weight. In the 2‐F‐L‐a‐treated mice, PDGFRα, PAR2, and Ki‐67 coexpression was increased and PDGFRα and PAR2 mRNA and protein expression was significantly enhanced in the colonic smooth muscle layer. 2‐F‐L‐a also increased proliferation and PDGFRα expression in NIH/3T3 cells cultured in high glucose, while LY294002, a PI3K antagonist, decreased cell proliferation and PDGFRα expression. PI3K and Akt protein and mRNA expression and p‐Akt protein expression in diabetic and 2‐F‐L‐a‐treated mice were markedly reduced in colonic smooth muscle. 2‐F‐L‐a also reduced PI3K, Akt, and p‐Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα+ cells through the PI3K/Akt signaling pathway in the colon of STZ‐induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes.
format	article
author	Yu‐Jia Li Jun‐Ping Ao Xu Huang Hong‐Li Lu Han‐Yue Fu Ni‐Na Song Wen‐Xie Xu Jie Chen
author_facet	Yu‐Jia Li Jun‐Ping Ao Xu Huang Hong‐Li Lu Han‐Yue Fu Ni‐Na Song Wen‐Xie Xu Jie Chen
author_sort	Yu‐Jia Li
title	Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
title_short	Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
title_full	Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
title_fullStr	Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
title_full_unstemmed	Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
title_sort	involvement of par2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e425ff118a0645f8b39367ef3322523a
work_keys_str_mv	AT yujiali involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT junpingao involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT xuhuang involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT honglilu involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT hanyuefu involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT ninasong involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT wenxiexu involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice AT jiechen involvementofpar2inplateletderivedgrowthfactorreceptorapositivecellproliferationinthecolonofdiabeticmice
_version_	1718428466935758848

Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice

Ejemplares similares