罗沙司他通过上调 TLR4 来保护小鼠免受 DSS 诱导的结肠炎。
Roxadustat protect mice from DSS-induced colitis in vivo by up-regulation of TLR4.
机构信息
School of Public Health and Management, Wenzhou Medical University, Zhejiang Province 325000, China; Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
出版信息
Genomics. 2023 Mar;115(2):110585. doi: 10.1016/j.ygeno.2023.110585. Epub 2023 Feb 19.
BACKGROUND
The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. The role of the PHD-HIF pathway in relieving DSS-induced colitis is gradually being explored.
METHODS
Wild-type C57BL/6 mice were used as a model of DSS-induced colitis to explore the important role of Roxadustat in alleviating DSS-induced colitis. High-throughput RNA-Seq and qRT-PCR methods were used to screen and verify the key differential genes in the colon of mice between normal saline (NS) and Roxadustat groups.
RESULTS
Roxadustat could alleviate DSS-induced colitis. Compared with the mice in the NS group, TLR4 were significantly up-regulated in the Roxadustat group. TLR4 KO mice were used to verify the role of TLR4 in the alleviation of DSS-induced colitis by Roxadustat.
CONCLUSION
Roxadustat has a repairing effect on DSS-induced colitis, and may alleviate DSS-induced colitis by targeting the TLR4 pathway and promote intestinal stem cell proliferation.
背景
炎症性肠病（IBD）的发病率在人群中不断增加。目前，炎症性肠病的病因仍不清楚，也没有有效且低毒的治疗药物。PHD-HIF 通路在缓解 DSS 诱导的结肠炎中的作用正逐渐被探索。
方法
以野生型 C57BL/6 小鼠为 DSS 诱导结肠炎模型，探讨罗沙司他对 DSS 诱导结肠炎的缓解作用。采用高通量 RNA-Seq 和 qRT-PCR 方法筛选和验证正常生理盐水（NS）组和罗沙司他组小鼠结肠中的关键差异基因。
结果
罗沙司他可缓解 DSS 诱导的结肠炎。与 NS 组小鼠相比，Roxadustat 组 TLR4 明显上调。使用 TLR4 KO 小鼠验证罗沙司他通过 TLR4 通路缓解 DSS 诱导结肠炎的作用。
结论
罗沙司他对 DSS 诱导的结肠炎具有修复作用，可能通过靶向 TLR4 通路促进肠干细胞增殖，从而缓解 DSS 诱导的结肠炎。
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