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Knockdown of ghrelin-O-acyltransferase attenuates colitis through the modulation of inflammatory factors and tight junction proteins in the intestinal epithelium.
Cell Biology International ( IF 3.9 ) Pub Date : 2020-04-13 , DOI: 10.1002/cbin.11362
Peiying Tian 1 , Xiaolan Lu 1 , Nuyun Jin 1 , Jianping Shi 1
Affiliation  

Ghrelin‐O‐acyltransferase (GOAT) is a membrane‐bound enzyme that attaches eight‐carbon octanoate to a serine residue in ghrelin and thereby acylates inactive ghrelin to produce active ghrelin. In this study, we investigated the function of GOAT in the intestinal mucosal barrier. The intestinal mucosal barrier prevents harmful substances such as bacteria and endotoxin from entering the other tissues, organs, and blood circulation through the intestinal mucosa. Here, we established 5% dextran sodium sulfate (DSS)‐induced colitis in mice and found that the body weight and colon weight were significantly decreased in these mice. Furthermore, increased inflammation and apoptosis were observed in the tissues of DSS‐induced colitis mice, with increased expression of tumor necrosis factor‐α, interleukin‐6, phosphorylation of nuclear factor kappa B‐p65 (p‐NF‐κB‐p65), and cleaved caspase‐3, and decreased expression of tight junction (TJ) proteins such as zonula occluden‐1 and occludin. The knockdown of GOAT significantly attenuated colitis‐induced inflammation responses and apoptosis, while GOAT overexpression significantly enhanced the induction of colitis. These results suggest that knockdown of GOAT may attenuate colitis‐induced inflammation, ulcers, and fecal occult blood by decreasing the intestinal mucosal permeability via the modulation of inflammatory factors and TJ proteins.

中文翻译:

ghrelin-O-酰基转移酶的抑制可通过调节肠上皮中的炎症因子和紧密连接蛋白来减轻结肠炎。

Ghrelin- O酰基转移酶(GOAT)是一种膜结合酶,可将八碳辛酸与生长素释放肽的丝氨酸残基连接,从而酰化无活性的生长素释放肽,从而产生活性的生长素释放肽。在这项研究中,我们调查了GOAT在肠粘膜屏障中的功能。肠粘膜屏障可防止有害物质(例如细菌和内毒素)通过肠粘膜进入其他组织,器官和血液循环。在这里,我们在小鼠中建立了5%葡聚糖硫酸钠(DSS)诱发的结肠炎,并发现这些小鼠的体重和结肠重量显着降低。此外,在DSS诱导的结肠炎小鼠组织中观察到炎症和凋亡增加,肿瘤坏死因子α,白介素6,核因子κB-p65(p-NF-κB-p65)的磷酸化和裂解的半胱天冬酶-3的表达,并降低紧密连接(TJ)蛋白的表达,例如小带闭合蛋白-1和闭合蛋白。GOAT的抑制显着减弱了结肠炎诱导的炎症反应和细胞凋亡,而GOAT的过表达显着增强了结肠炎的诱导。这些结果表明,通过调节炎症因子和TJ蛋白可降低肠道粘膜通透性,降低GOAT可能会减轻结肠炎诱发的炎症,溃疡和粪便潜血。而GOAT的过表达显着增强了结肠炎的诱导。这些结果表明,通过调节炎症因子和TJ蛋白可降低肠道粘膜通透性,降低GOAT可能会减轻结肠炎诱发的炎症,溃疡和粪便潜血。而GOAT的过表达显着增强了结肠炎的诱导。这些结果表明,通过调节炎症因子和TJ蛋白可降低肠道粘膜通透性,降低GOAT可能会减轻结肠炎诱发的炎症,溃疡和粪便潜血。
更新日期:2020-04-13
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