School of Life Science and Technology, Tongji University, Shanghai, 200092 China.
Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
Cell Biosci. 2015 Mar 21;5:12. doi: 10.1186/s13578-015-0002-5. eCollection 2015.
Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development.
The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro.
Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.
GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.
生长激素促分泌素受体（GHSR）及其配体 ghrelin 是体重控制和能量稳态的重要调节剂。最近，ghrelin 也参与了实验性结肠炎，但 GHSR 在结肠炎发展中的作用尚不清楚。本研究旨在探讨 GHSR 在炎症性肠病（IBD）发展中的潜在机制。
在葡聚糖硫酸钠（DSS）诱导的 Wt 小鼠结肠炎中，测定 GHSR/ghrelin 的时间表达。比较 GHSR（-/-）和 Wt 小鼠 DSS 诱导结肠炎的临床/病理严重程度。此外，还在体内和体外评估了巨噬细胞的功能。
缺乏 GHSR 可显著减轻临床和病理水平的结肠炎，结肠促炎细胞因子减少（P<0.05）。这与 DSS 处理的 GHSR（-/-）小鼠比 Wt 小鼠的结肠巨噬细胞浸润和 TLRs 表达减少的观察结果一致（P<0.05）。此外，与 Wt 小鼠相比，GHSR（-/-）小鼠 LPS 刺激的巨噬细胞中促炎细胞因子明显减少（P<0.05）。此外，D-lys（3）-GHRP6（一种 GHSR 拮抗剂）可减少体外 LPS 诱导的 Wt 小鼠巨噬细胞促炎细胞因子。
GHSR 有助于急性 DSS 诱导的结肠炎的发展，可能通过升高的促炎细胞因子和巨噬细胞的激活。这些数据表明 GHSR 可能是 IBD 的一个潜在治疗靶点。
