PMID- 34620946
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20240226
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Oct 7
TI  - Irbesartan, an angiotensin II type 1 receptor blocker, inhibits 
      colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.
PG  - 19943
LID - 10.1038/s41598-021-99412-8 [doi]
LID - 19943
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Hachiya, Kensuke
AU  - Hachiya K
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Masuya, Masahiro
AU  - Masuya M
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan. mmasuya@med.mie-u.ac.jp.
AD  - Course of Nursing Science, Mie University Graduate School of Medicine, 2-174 
      Edobashi, Tsu, Mie, 514-8507, Japan. mmasuya@med.mie-u.ac.jp.
FAU - Kuroda, Naoki
AU  - Kuroda N
AD  - Department of Gastroenterology, Saiseikai Matsusaka General Hospital, Matsusaka, 
      Mie, 515-8557, Japan.
FAU - Yoneda, Misao
AU  - Yoneda M
AD  - Department of Clinical Nutrition Medical Technology Course, Suzuka University of 
      Medical Science, Suzuka, Mie, 510-0293, Japan.
FAU - Tsuboi, Junya
AU  - Tsuboi J
AD  - Department of Gastroenterology and Hepatology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Nagaharu, Keiki
AU  - Nagaharu K
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Nishimura, Komei
AU  - Nishimura K
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Shiotani, Takuya
AU  - Shiotani T
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Ohishi, Kohshi
AU  - Ohishi K
AD  - Department of Transfusion Medicine and Cell Therapy, Mie University Hospital, 
      Tsu, Mie, 514-8507, Japan.
FAU - Tawara, Isao
AU  - Tawara I
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
FAU - Katayama, Naoyuki
AU  - Katayama N
AD  - Department of Haematology and Oncology, Mie University Graduate School of 
      Medicine, Tsu, Mie, 514-8507, Japan.
AD  - Faculty of Nursing, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211007
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - J0E2756Z7N (Irbesartan)
RN  - MO0N1J0SEN (Azoxymethane)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Animals
MH  - Azoxymethane
MH  - Carcinogenesis
MH  - Chemokine CCL2/metabolism
MH  - Colitis/chemically induced/*complications
MH  - Colonic Neoplasms/complications/*etiology
MH  - Dextran Sulfate
MH  - Irbesartan/*pharmacology
MH  - Mice, Inbred C57BL
MH  - Receptors, CCR2/genetics
MH  - Mice
PMC - PMC8497524
COIS- The authors declare no competing interests.
EDAT- 2021/10/09 06:00
MHDA- 2022/01/13 06:00
PMCR- 2021/10/07
CRDT- 2021/10/08 06:45
PHST- 2021/07/12 00:00 [received]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/10/08 06:45 [entrez]
PHST- 2021/10/09 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/10/07 00:00 [pmc-release]
AID - 10.1038/s41598-021-99412-8 [pii]
AID - 99412 [pii]
AID - 10.1038/s41598-021-99412-8 [doi]
PST - epublish
SO  - Sci Rep. 2021 Oct 7;11(1):19943. doi: 10.1038/s41598-021-99412-8.