Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Muellner Hauptstr. 48, 5020, Salzburg, Austria.
Research Unit of Translational Neurogastroenterology, Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria.
Sci Rep. 2021 Jan 12;11(1):564. doi: 10.1038/s41598-020-79456-y.
The regulatory (neuro)peptide galanin and its three receptors (GALR) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GALR and GALR contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn's disease and ulcerative colitis) expressed GALR and GALR but not GALR. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GALR (GALR-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GALR resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GALR-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GALR deletion did not influence the course of colitis. In conclusion, granulocyte GALR and GALR expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GALR loss. Consequently, GALR poses a novel therapeutic target for IBD.
调节（神经）肽甘丙肽及其三种受体（GALR）参与免疫和炎症。甘丙肽可减轻大鼠的炎症性肠病（IBD）。然而，涉及甘丙肽受体的研究还很缺乏。我们旨在确定 IBD 患者中甘丙肽受体的表达，并评估 GALR 和 GALR 是否有助于小鼠结肠炎。免疫组织化学分析显示，IBD 患者（克罗恩病和溃疡性结肠炎）结肠标本中的粒细胞表达 GALR 和 GALR，但不表达 GALR。用 2%葡聚糖硫酸钠（DSS）诱导 7 天后，缺乏 GALR 的小鼠（GALR-KO）体重减轻更多，表现出更严重的结肠炎症和更严重的组织学损伤，与野生型动物相比，中性粒细胞浸润增加。GALR 的缺失导致局部和全身炎症细胞因子/趋化因子水平升高。值得注意的是，通过定量非培养技术评估的与结肠炎相关的肠道微生物组变化在 GALR-KO 小鼠中最为明显，其特征是肠杆菌和双歧杆菌数量增加。相比之下，GALR 的缺失并不影响结肠炎的病程。总之，粒细胞 GALR 和 GALR 的表达与人类的 IBD 活动有关，DSS 诱导的小鼠结肠炎受 GALR 缺失的强烈影响。因此，GALR 是 IBD 的一个新的治疗靶点。
