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DOCK4 regulates ghrelin production in gastric X/A-like cells

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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.

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Data availability

All data relevant to the study are included in the article or uploaded as supplemental information.

Code availability

Not applicable.

Abbreviations

GHSR:

Growth hormone secretagogue receptor

DOCK4:

Dedicator of cytokinesis 4

GEFs:

Guanine nucleotide exchange factors

ASD:

Autism spectrum disorder

AD:

Alzheimer’s disease

mHypoE-42:

Embryonic mouse hypothalamic cell line N42

RT:

Reverse transcription

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82170818, 81770794), the Key-Area Research and Development Program of Guangdong Province (2019B030335001), the Fundamental Research Funds for the Central Universities (21620423).

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Author notes

  1. Y. Huang and Y. Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou, 510632, Guangdong, China

    Y. Huang, Y. Zhao, L. Chen & G. Xu

  2. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China

    Y. Yang, D. Guo & L. Shi

  3. The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China

    D. Guo

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Contributions

Geyang Xu and Lei Shi designed research; Yanling Huang, Yaorong Yang, Daji Guo, Yawen Zhao and Linxi Chen performed research; Geyang Xu and Lei Shi analyzed data; Yanling Huang and Yaorong Yang wrote and edited the paper. All authors contributed to the discussion and revised the article and all approved the final versions of the manuscript. Geyang Xu is responsible for the integrity of the work as a whole.

Corresponding authors

Correspondence to L. Shi or G. Xu.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1.

Ethics approval

Animals used in this study were handled in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publications No. 8023, revised 1978). All animal protocols were approved by the Animal Care and Use Committee of Jinan University. Participation in this study was voluntary and written informed consent was obtained from each participant. The guidelines of the Declaration of Helsinki of the World Medical Association were followed. All protocols were approved by the Research Ethics Committee of the First Affiliated Hospital of Jinan University.

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Huang, Y., Yang, Y., Zhao, Y. et al. DOCK4 regulates ghrelin production in gastric X/A-like cells. J Endocrinol Invest 45, 1447–1454 (2022). https://doi.org/10.1007/s40618-022-01785-8

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  • DOI: https://doi.org/10.1007/s40618-022-01785-8

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