Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
Am J Physiol Cell Physiol. 2020 Mar 1;318(3):C502-C513. doi: 10.1152/ajpcell.00454.2019. Epub 2020 Jan 8.
Olfactory receptor-78 (Olfr-78) is a recently identified G protein-coupled receptor activated by short-chain fatty acids acetate and propionate. A suggested role for this receptor exists in the prostate where it may influence chronic inflammatory response leading to intraepithelial neoplasia. Olfr-78 has also been shown to be expressed in mouse colon. Short-chain fatty acids and their receptors are well known to modulate inflammation in the gut. Considering this possibility, we first explored if colitis regulated Olfr-78 expression in the gut, where we observed a significant reduction in the expression of Olfr-78 transcript in mouse models of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. To more directly test this, mice deficient in Olfr-78 were administered with DSS in water for 7 days and were found to have increased expression of IL-1β and inflammatory signs in colon compared with control mice. Next, we explored the expression of its human counterpart olfactory receptor family 51, subfamily E, member 2 (OR51E2) in human intestinal samples and observed that it was in fact also expressed in human colon samples. RNA sequence analysis revealed significant changes in the genes involved in infection, immunity, inflammation, and colorectal cancer between wild-type and Olfr-78 knockout mice. Collectively, our findings show that Olfr-78 is highly expressed in colon and downregulated in DSS- and TNBS-induced colitis, and DSS-treated Olfr-78 null mice had increased colonic expression of cytokine RNA levels, suggesting a potential role for this receptor in intestinal inflammation. Future investigations are needed to understand how Olfr-78/OR51E2 in both mouse and human intestine modulates gastrointestinal pathophysiology.
嗅觉受体 78（Olfr-78）是一种新发现的 G 蛋白偶联受体，可被短链脂肪酸乙酸盐和丙酸盐激活。该受体在前列腺中可能发挥作用，影响慢性炎症反应，导致上皮内瘤变。该受体也在小鼠结肠中表达。短链脂肪酸及其受体已被证实可调节肠道炎症。考虑到这种可能性，我们首先探讨了结肠炎是否调节肠道中的 Olfr-78 表达，在葡聚糖硫酸钠（DSS）和 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎小鼠模型中，我们观察到 Olfr-78 转录本的表达显著降低。为了更直接地测试这一点，用 DSS 处理缺乏 Olfr-78 的小鼠 7 天，并发现与对照小鼠相比，其结肠中 IL-1β 和炎症标志物的表达增加。接下来，我们研究了其人类同源物嗅觉受体家族 51，亚家族 E，成员 2（OR51E2）在人类肠道样本中的表达，结果发现它实际上也在人类结肠样本中表达。RNA 序列分析显示，野生型和 Olfr-78 敲除小鼠之间涉及感染、免疫、炎症和结直肠癌的基因表达发生显著变化。总之，我们的研究结果表明，Olfr-78 在结肠中高度表达，在 DSS 和 TNBS 诱导的结肠炎中下调，并用 DSS 处理的 Olfr-78 缺失小鼠的结肠细胞因子 RNA 水平表达增加，提示该受体在肠道炎症中可能发挥作用。需要进一步的研究来了解 Olfr-78/OR51E2 在小鼠和人类肠道中如何调节胃肠道病理生理学。
