Somatostatin receptor 5 (SSTR5) is involved in intestinal barrier protection during colitis through modulating tight junction (TJ) proteins, but the mechanisms of SSTR5 in TJ regulation are largely unknown. Therefore, the present study was designed to illuminate how SSTR5 modulated intestinal barrier function and TJ proteins. In this study, activation of SSTR5 by its special agonist L817,818 effectively ameliorated impaired intestinal barrier function in TNF-α-pretreated cells and mice with colitis. Restoration of intestinal barrier function was dependent on upregulation of claudin-4 and ZO-1. Suppression of SSTR5 signaling through specific siRNA or the antagonist BIM23056 markedly exacerbated TNF-α-induced claudin-4 and ZO-1 damage. L817,818 treatment markedly suppressed TNF-α-induced NF-κB p65 phosphorylation, myosin light chain kinase (MLCK) upregulation and myosin light chain (MLC) phosphorylation. Exposure to a NF-κB inhibitor (QNZ) or MLCK inhibitor (ML-7) effectively inhibited compromised claudin-4 and ZO-1 induced by BIM23056/TNF-α. These observations indicate that activation of SSTR5 protects intestinal barrier function by upregulating claudin-4 and ZO-1 expression, which is mediated by NF-κB-MLCK-MLC signaling. Taken together, our findings suggest that SSTR5 might represent a promising target for colitis therapy.

生长抑素受体 5 (SSTR5) 通过调节紧密连接 (TJ) 蛋白参与结肠炎期间的肠道屏障保护，但 SSTR5 在 TJ 调节中的机制在很大程度上是未知的。因此，本研究旨在阐明 SSTR5 如何调节肠道屏障功能和 TJ 蛋白。在这项研究中，其特殊激动剂 L817,818 激活 SSTR5 可有效改善 TNF-α 预处理细胞和结肠炎小鼠肠道屏障功能受损。肠屏障功能的恢复依赖于claudin-4和ZO-1的上调。通过特异性 siRNA 或拮抗剂 BIM23056 抑制 SSTR5 信号传导显着加剧了 TNF-α 诱导的 claudin-4 和 ZO-1 损伤。L817,818 处理显着抑制 TNF-α 诱导的 NF-κB p65 磷酸化，肌球蛋白轻链激酶 (MLCK) 上调和肌球蛋白轻链 (MLC) 磷酸化。暴露于 NF-κB 抑制剂 (QNZ) 或 MLCK 抑制剂 (ML-7) 可有效抑制 BIM23056/TNF-α 诱导的受损 claudin-4 和 ZO-1。这些观察结果表明，SSTR5 的激活通过上调由 NF-κB-MLCK-MLC 信号传导介导的 claudin-4 和 ZO-1 表达来保护肠道屏障功能。总之，我们的研究结果表明 SSTR5 可能代表结肠炎治疗的一个有希望的目标。这是由 NF-κB-MLCK-MLC 信号介导的。总之，我们的研究结果表明 SSTR5 可能代表结肠炎治疗的一个有希望的目标。这是由 NF-κB-MLCK-MLC 信号介导的。总之，我们的研究结果表明 SSTR5 可能代表结肠炎治疗的一个有希望的目标。