Y Huang1, Y Yang2, Y Zhao1, D Guo2,3, L Chen1, L Shi4, G Xu5. 1. Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, 510632, Guangdong, China. 2. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China. 3. The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China. 4. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China. sophielshi80@gmail.com. 5. Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, 510632, Guangdong, China. xugeyangliang@163.com.
Abstract
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.
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.
Authors: T D Müller; R Nogueiras; M L Andermann; Z B Andrews; S D Anker; J Argente; R L Batterham; S C Benoit; C Y Bowers; F Broglio; F F Casanueva; D D'Alessio; I Depoortere; A Geliebter; E Ghigo; P A Cole; M Cowley; D E Cummings; A Dagher; S Diano; S L Dickson; C Diéguez; R Granata; H J Grill; K Grove; K M Habegger; K Heppner; M L Heiman; L Holsen; B Holst; A Inui; J O Jansson; H Kirchner; M Korbonits; B Laferrère; C W LeRoux; M Lopez; S Morin; M Nakazato; R Nass; D Perez-Tilve; P T Pfluger; T W Schwartz; R J Seeley; M Sleeman; Y Sun; L Sussel; J Tong; M O Thorner; A J van der Lely; L H T van der Ploeg; J M Zigman; M Kojima; K Kangawa; R G Smith; T Horvath; M H Tschöp Journal: Mol Metab Date: 2015-03-21 Impact factor: 7.422