DOCK4调节胃X/A样细胞中胃饥饿素的产生。
DOCK4 regulates ghrelin production in gastric X/A-like cells.
作者信息
Huang Y, Yang Y, Zhao Y, Guo D, Chen L, Shi L, Xu G
机构信息
Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, 510632, Guangdong, China.
JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China.
出版信息
J Endocrinol Invest. 2022 Jul;45(7):1447-1454. doi: 10.1007/s40618-022-01785-8. Epub 2022 Mar 17.
PURPOSE
Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Ghrelin also modulates neuroinflammatory and apoptotic processes. Dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF), is involved in the regulation of neuronal polarization and axon regeneration. However, the effect of DOCK4 on ghrelin production has not been explored.
METHODS
The expression of DOCK4 in human and mouse stomach was examined by immunohistochemical staining. The synthesis and secretion of ghrelin in Dock4 null mice were evaluated by real-time quantitative PCR, Western blot and ELISA. The effects of DOCK4 on ghrelin production in mHypoE-42 cells were measured by real-time quantitative PCR and Western blot.
RESULTS
We showed that DOCK4 was expressed in both human and mouse gastric ghrelin cells. The mRNA and protein levels of gastric ghrelin, as well as ghrelin secretion, were remarkably diminished in Dock4 null mice. Furthermore, we showed that overexpression of Dock4 significantly stimulated ghrelin expression, while siRNA knockdown of endogenous Dock4 resulted in a marked decrease of ghrelin in mHypoE-N42 cells.
CONCLUSIONS
Our results identify DOCK4 as a critical regulator for ghrelin production in gastric X/A-like cells.
目的
胃饥饿素是一种胃激素，可向中枢神经系统传递饥饿信号以刺激食物摄入。胃饥饿素还可调节神经炎症和凋亡过程。胞质分裂 dedicator 4（DOCK4）是一种鸟嘌呤核苷酸交换因子（GEF），参与神经元极化和轴突再生的调节。然而，DOCK4 对胃饥饿素产生的影响尚未得到研究。
方法
通过免疫组织化学染色检测 DOCK4 在人和小鼠胃中的表达。通过实时定量 PCR、蛋白质印迹法和酶联免疫吸附测定法评估 Dock4 基因敲除小鼠中胃饥饿素的合成和分泌。通过实时定量 PCR 和蛋白质印迹法测定 DOCK4 对 mHypoE-42 细胞中胃饥饿素产生的影响。
结果
我们发现 DOCK4 在人和小鼠胃中的胃饥饿素细胞中均有表达。Dock4 基因敲除小鼠中胃饥饿素的 mRNA 和蛋白质水平以及胃饥饿素分泌均显著降低。此外，我们发现 DOCK4 的过表达显著刺激胃饥饿素表达，而内源性 Dock4 的 siRNA 敲低导致 mHypoE-N42 细胞中胃饥饿素显著减少。
结论
我们的结果确定 DOCK4 是胃 X/A 样细胞中胃饥饿素产生的关键调节因子。
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