Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.
Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.
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厄贝沙坦是一种血管紧张素II 1型受体阻滞剂，通过阻断MCP-1/CCR 2途径抑制结肠炎相关的肿瘤发生。
DOI：
10.1038/s41598-021-99412-8
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发表时间：
2021-10-07
影响因子：
4.6
通讯作者：
Katayama N
中科院分区：
文献类型：
--
作者：
Hachiya K;Masuya M;Kuroda N;Yoneda M;Tsuboi J;Nagaharu K;Nishimura K;Shiotani T;Ohishi K;Tawara I;Katayama N
抗炎疗法的引入使得炎症性肠病（IBD）患者的疾病活动性得到实质性改善。然而，IBD可导致严重的并发症，如肠纤维化和结直肠癌。因此，需要减少这些并发症发展的新疗法。血管紧张素II（Ang II）通过刺激单核细胞趋化蛋白-1（MCP-1）或促炎细胞因子的产生来促进组织炎症。它在IBD进展中起着关键作用。虽然已经报道了阻断Ang II可以改善实验性结肠炎并降低结直肠癌风险，但其细胞和分子机制仍然知之甚少。我们之前的工作表明，厄贝沙坦（一种血管紧张素II 1型受体阻滞剂）可以减少炎症胰腺中C-C趋化因子受体2阳性（CCR 2+）单核细胞的数量。本研究旨在使用氧化偶氮甲烷/葡聚糖硫酸钠小鼠模型研究厄贝沙坦可能的抗纤维化和抗肿瘤作用。厄贝沙坦抑制炎症结肠中MCP-1的产生和Ly 6C + CCR 2+单核细胞和纤维细胞的积累，下调1型胶原和基质金属蛋白酶9的表达，并抑制肠纤维化和肿瘤的发展。我们的观察表明，使用厄贝沙坦阻断MCP-1/CCR 2通路可能有助于预防结肠炎相关的结肠肿瘤。
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.
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影响因子：
3.3
作者：
Kohno, Takashi;Anzai, Toshihisa;Ogawa, Satoshi
通讯作者：
Ogawa, Satoshi
影响因子：
4.6
作者：
Kuroda, Naoki;Masuya, Masahiro;Katayama, Naoyuki
通讯作者：
Katayama, Naoyuki
DOI：
10.1177/1470320319895646
发表时间：
2020-07-01
影响因子：
2.9
作者：
Chen, Xia;Yi, Chang-hong;Ya, Kuang-guan
通讯作者：
Ya, Kuang-guan
影响因子：
5.7
作者：
BUCALA, R;SPIEGEL, LA;CERAMI, A
通讯作者：
CERAMI, A
影响因子：
4.6
作者：
Luis Miguel-Carrasco, Jose;Beaumont, Javier;Ravassa, Susana
通讯作者：
Ravassa, Susana