Velázquez Esther, Le Baut Ayuso Yannick, Blázquez Enrique, Ruiz-Albusac Juan Miguel
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Health Research Institute of the San Carlos Clinical Hospital, Madrid, Spain.
J Alzheimers Dis Rep. 2022 Nov 22;6(1):723-732. doi: 10.3233/ADR-220043. eCollection 2022.
Glucagon-like peptide-2 (GLP-2) is an intestinal trophic factor that induces astrocyte proliferation through its own receptor (GLP-2R), but the control of its expression is not well known.
To study the effects of glucose and of different mitogenic agents on the control of GLP-2R expression in cultured rat astrocytes.
GLP-2R mRNA content was measured by quantitative RT-PCR.
GLP-2R expression was higher in proliferating than in resting cells. The expression was dependent of glucose concentration both in the absence and in the presence of GLP-2. In the presence of a high glucose concentration, GLP-2, PDGF, and PDGF plus GLP-2 presented opposite effects depending on the incubation time. However, insulin, IGF-1, and EGF alone, and plus GLP-2 had no effect. IGF-2, but not IGF-2 plus GLP-2, increased the expression. On the contrary, NGF decreased the GLP-2R expression, but NGF plus GLP-2 increased it even until values similar to those obtained with GLP-2 alone. Interestingly, in the presence of a low glucose concentration, leptin and NPY produced a significant reduction of GLP-2R expression.
Astrocytes are distributed throughout the brain, where GLP-2 appears to have important functions. Since these cells express the GLP-2R, the results of this study could be considered of interest to advance the knowledge of the role of GLP-2 signaling in the CNS, which should lead a better understanding of the events that occur under normal and pathophysiological conditions.
胰高血糖素样肽-2（GLP-2）是一种肠营养因子，可通过其自身受体（GLP-2R）诱导星形胶质细胞增殖，但其表达的调控尚不清楚。
研究葡萄糖和不同促有丝分裂剂对培养的大鼠星形胶质细胞中GLP-2R表达调控的影响。
通过定量逆转录聚合酶链反应（RT-PCR）检测GLP-2R mRNA含量。
增殖细胞中GLP-2R的表达高于静息细胞。无论有无GLP-2，其表达均依赖于葡萄糖浓度。在高葡萄糖浓度下，GLP-2、血小板衍生生长因子（PDGF）以及PDGF加GLP-2根据孵育时间呈现相反的作用。然而，单独的胰岛素、胰岛素样生长因子-1（IGF-1）和表皮生长因子（EGF）以及它们加GLP-2均无作用。IGF-2可增加表达，但IGF-2加GLP-2则无此作用。相反，神经生长因子（NGF）降低GLP-2R表达，但NGF加GLP-2可增加其表达，甚至达到与单独使用GLP-2时相似的值。有趣的是，在低葡萄糖浓度下，瘦素和神经肽Y（NPY）可显著降低GLP-2R表达。
星形胶质细胞分布于整个大脑，GLP-2在其中似乎具有重要功能。由于这些细胞表达GLP-2R，本研究结果可能有助于推进对GLP-2信号在中枢神经系统中作用的认识，从而更好地理解正常和病理生理条件下发生的事件。
