IDDF2024-ABS-0214 G protein-coupled receptor 68 deficiency alleviates sepsis-induced intestinal injury

<h3>Background</h3> Sepsis is a life-threatening multi-organ dysfunction syndrome caused by uncontrolled infection. Intestinal barrier dysfunction during sepsis promotes the spreading of infection and drives the development of organ dysfunction. G protein-coupled receptor 68 (GPR68) is an acid and mechanosensitive receptor that plays a vital role in various physiological and pathological processes. However, the role of GPR68 in sepsis-induced intestinal injury remains unclear. <h3>Methods</h3> Cecal ligation and puncture (CLP) and intraperitoneal injection of lipopolysaccharide (LPS) were used to establish the sepsis model in GPR68 knockout (GPR68-KO) and wildtype (WT) mice. The expression levels of intestinal barrier function markers (zonula occludens-1 [ZO-1], claudins, occludins) and inflammatory cytokines were assessed using qRT-PCR. The severity of sepsis and intestinal injury in mice was evaluated through the sepsis score and Chiu’s score. Kaplan-Meier curves and log-rank tests were used to compare the mortality. <h3>Results</h3> Compared to the baseline, the mRNA expression level of GPR68 was significantly upregulated in the intestinal tissues of CLP- and LPS-induced sepsis mice, which positively correlated with the levels of pro-inflammatory cytokines. In comparison to WT mice, GPR68-KO sepsis mice showed decreased 24-hour mortality rates (GPR68-KO vs WT, 35.29% vs 68.42%, P = 0.01). The sepsis score and intestinal Chiu’s score were also lower in KO mice. The expression of intestinal barrier function markers ZO-1, claudin-1, occludin-1 was significantly preserved in GPR68 KO mice compared to WT. <h3>Conclusions</h3> GPR68 deficiency alleviates the mortality, intestinal tissue damage and barrier protein expression in sepsis-induced intestinal injury, suggesting that GPR68 participates in the pathological process of sepsis in the small intestine.