Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway

Abstract The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kensuke Hachiya, Masahiro Masuya, Naoki Kuroda, Misao Yoneda, Junya Tsuboi, Keiki Nagaharu, Komei Nishimura, Takuya Shiotani, Kohshi Ohishi, Isao Tawara, Naoyuki Katayama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e58d64e9edc74af080a895f2e1df1344
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e58d64e9edc74af080a895f2e1df1344
record_format	dspace
spelling	oai:doaj.org-article:e58d64e9edc74af080a895f2e1df13442021-12-02T18:37:09ZIrbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway10.1038/s41598-021-99412-82045-2322https://doaj.org/article/e58d64e9edc74af080a895f2e1df13442021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99412-8https://doaj.org/toc/2045-2322Abstract The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing the development of these complications are needed. Angiotensin II (Ang II) promotes tissue inflammation by stimulating the production of monocyte chemoattractant protein-1 (MCP-1) or proinflammatory cytokines. It plays a pivotal role in IBD progression. Although blockade of Ang II has been reported to ameliorate experimental colitis and reduce colorectal cancer risk, the cellular and molecular mechanisms remain poorly understood. Our previous work showed that irbesartan, an Ang II type 1 receptor blocker, reduced the number of C–C chemokine receptor 2-positive (CCR2+) monocytic cells in the inflamed pancreas. This study aimed to investigate the possible antifibrotic and antitumour effects of irbesartan using the azoxymethane/dextran sodium sulphate mouse model. Irbesartan suppressed MCP-1 production and the accumulation of Ly6C+CCR2+ monocytes and fibrocytes in the inflamed colon, downregulated the expression of type 1 collagen and matrix metalloproteinase 9 and inhibited the development of intestinal fibrosis and tumours. Our observations suggest that blocking the MCP-1/CCR2 pathway using irbesartan might be beneficial in preventing colitis-associated colon tumours.Kensuke HachiyaMasahiro MasuyaNaoki KurodaMisao YonedaJunya TsuboiKeiki NagaharuKomei NishimuraTakuya ShiotaniKohshi OhishiIsao TawaraNaoyuki KatayamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kensuke Hachiya Masahiro Masuya Naoki Kuroda Misao Yoneda Junya Tsuboi Keiki Nagaharu Komei Nishimura Takuya Shiotani Kohshi Ohishi Isao Tawara Naoyuki Katayama Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
description	Abstract The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing the development of these complications are needed. Angiotensin II (Ang II) promotes tissue inflammation by stimulating the production of monocyte chemoattractant protein-1 (MCP-1) or proinflammatory cytokines. It plays a pivotal role in IBD progression. Although blockade of Ang II has been reported to ameliorate experimental colitis and reduce colorectal cancer risk, the cellular and molecular mechanisms remain poorly understood. Our previous work showed that irbesartan, an Ang II type 1 receptor blocker, reduced the number of C–C chemokine receptor 2-positive (CCR2+) monocytic cells in the inflamed pancreas. This study aimed to investigate the possible antifibrotic and antitumour effects of irbesartan using the azoxymethane/dextran sodium sulphate mouse model. Irbesartan suppressed MCP-1 production and the accumulation of Ly6C+CCR2+ monocytes and fibrocytes in the inflamed colon, downregulated the expression of type 1 collagen and matrix metalloproteinase 9 and inhibited the development of intestinal fibrosis and tumours. Our observations suggest that blocking the MCP-1/CCR2 pathway using irbesartan might be beneficial in preventing colitis-associated colon tumours.
format	article
author	Kensuke Hachiya Masahiro Masuya Naoki Kuroda Misao Yoneda Junya Tsuboi Keiki Nagaharu Komei Nishimura Takuya Shiotani Kohshi Ohishi Isao Tawara Naoyuki Katayama
author_facet	Kensuke Hachiya Masahiro Masuya Naoki Kuroda Misao Yoneda Junya Tsuboi Keiki Nagaharu Komei Nishimura Takuya Shiotani Kohshi Ohishi Isao Tawara Naoyuki Katayama
author_sort	Kensuke Hachiya
title	Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
title_short	Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
title_full	Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
title_fullStr	Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
title_full_unstemmed	Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
title_sort	irbesartan, an angiotensin ii type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the mcp-1/ccr2 pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e58d64e9edc74af080a895f2e1df1344
work_keys_str_mv	AT kensukehachiya irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT masahiromasuya irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT naokikuroda irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT misaoyoneda irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT junyatsuboi irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT keikinagaharu irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT komeinishimura irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT takuyashiotani irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT kohshiohishi irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT isaotawara irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway AT naoyukikatayama irbesartananangiotensiniitype1receptorblockerinhibitscolitisassociatedtumourigenesisbyblockingthemcp1ccr2pathway
_version_	1718377833534849024

Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway

Ejemplares similares