Mfge8 attenuates human gastric antrum smooth muscle contractions.


Journal

Journal of muscle research and cell motility
ISSN: 1573-2657
Titre abrégé: J Muscle Res Cell Motil
Pays: Netherlands
ID NLM: 8006298

Informations de publication

Date de publication:
06 2021
Historique:
received: 28 03 2021
accepted: 21 05 2021
pubmed: 5 6 2021
medline: 18 1 2022
entrez: 4 6 2021
Statut: ppublish

Résumé

Coordinated gastric smooth muscle contraction is critical for proper digestion and is adversely affected by a number of gastric motility disorders. In this study we report that the secreted protein Mfge8 (milk fat globule-EGF factor 8) inhibits the contractile responses of human gastric antrum muscles to cholinergic stimuli by reducing the inhibitory phosphorylation of the MYPT1 (myosin phosphatase-targeting subunit (1) subunit of MLCP (myosin light chain phosphatase), resulting in reduced LC20 (smooth muscle myosin regulatory light chain (2) phosphorylation. Mfge8 reduced the agonist-induced increase in the F-actin/G-actin ratios of β-actin and γ-actin1. We show that endogenous Mfge8 is bound to its receptor, α8β1 integrin, in human gastric antrum muscles, suggesting that human gastric antrum muscle mechanical responses are regulated by Mfge8. The regulation of gastric antrum smooth muscles by Mfge8 and α8 integrin functions as a brake on gastric antrum mechanical activities. Further studies of the role of Mfge8 and α8 integrin in regulating gastric antrum function will likely reveal additional novel aspects of gastric smooth muscle motility mechanisms.

Identifiants

pubmed: 34085177
doi: 10.1007/s10974-021-09604-y
pii: 10.1007/s10974-021-09604-y
pmc: PMC8332633
doi:

Substances chimiques

Antigens, Surface 0
MFGE8 protein, human 0
Milk Proteins 0
Myosin Light Chains 0
Myosin-Light-Chain Phosphatase EC 3.1.3.53

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

219-231

Subventions

Organisme : NIDDK NIH HHS
ID : U24 DK076169
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Wen Li (W)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.

Ashley Olseen (A)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.

Yeming Xie (Y)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
Bioinformatics, BGI Group, Shenzhen, Guangdon, China.

Cristina Alexandru (C)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.

Andrew Outland (A)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.

Angela F Herrera (AF)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.

Andrew J Syder (AJ)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical Company Limited, San Diego, CA, USA.

Jill Wykosky (J)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical Company Limited, San Diego, CA, USA.

Brian A Perrino (BA)

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. bperrino@med.unr.edu.

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Classifications MeSH