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纳林林通过抑制ER压力诱导的PAR2激活来缓解肠道纤维化

Jinguo Liu¹, Lei Xu², Li Wang³

¹Department of Endoscopy Center, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Inflammatory bowel diseases

|April 1, 2024

概括

纳林可以通过抑制ER压力和巨细胞激活来治疗克罗恩病中的肠道纤维化. 这项研究揭示了这种常见并发症的新治疗点.

科学领域:

胃肠病学胃肠病学
细胞生物学细胞生物学
药理学药理学是指药理学的学科.

背景情况:

肠道纤维化和狭窄性在克罗恩病 (CD) 中很常见,由于缺乏向抗纤维治疗,通常需要手术.
由X盒结合蛋白1 (XBP1) 介导的内质网膜 (ER) 应激作用,涉及质细胞脱粒化,蛋白酶激活受体2 (PAR2) 激活,以及随后的纤维化.
众所周知,纳林因 (NAR) 抑制ER压力并减少器官纤维化.

研究的目的:

调查ER应力杆细胞酸酶-PAR2轴在促进克罗恩病中肠道纤维化中的作用.
为了确定naringin (NAR) 是否通过抑制ER压力诱导的PAR2激活来表现出抗纤维作用.

主要方法:

在纤维性CD狭窄症中分析XBP1,巨细胞合酶和PAR2表达.
分子对接以模拟与拼接的XBP1.1的naringin相互作用.
在体外和体内实验中评估ER应激,杆细胞脱粒和PAR2激活对肠道纤维化的影响,有或没有纳林林治疗.
在F2rl1 (PAR2) 淘汰模型中评估naringin的抗纤维菌疗效.

主要成果:

在纤维性CD狭窄症中观察到XBP1,巨细胞合酶和PAR2的升高水平.
已经证明,ER压力刺激了巨细胞脱粒化,导致三酶释放,PAR2激活,上皮层-介质酶过渡和肠道纤维化.
纳林林治疗在体外和体内抑制了这些过程.
在肠道上皮细胞中删除F2rl1部分降低了naringin的抗纤维作用.

结论:

ER应激杆细胞酸酶-PAR2信号通路是克罗恩病中肠道纤维化的一个关键驱动因素.
纳林因通过准ER压力诱导的PAR2激活和缓解杆细胞脱粒化,显示出作为CD抗纤维菌剂的潜力.

关键词:

克罗恩氏病是什么克罗恩氏病是什么压力ERER压力ERER压力在PAR2中,PAR2是PAR2的一部分.肠道纤维化肠道纤维化在故事中,她讲述了她的故事.

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