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CD36 maintains the gastric mucosa and associates with gastric disease.

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cam.issuedOnline2021-11-02
dc.contributor.authorJacome-Sosa, Miriam
dc.contributor.authorMiao, Zhi-Feng
dc.contributor.authorPeche, Vivek S
dc.contributor.authorMorris, Edward F
dc.contributor.authorNarendran, Ramkumar
dc.contributor.authorPietka, Kathryn M
dc.contributor.authorSamovski, Dmitri
dc.contributor.authorLo, Hei-Yong G
dc.contributor.authorPietka, Terri
dc.contributor.authorVarro, Andrea
dc.contributor.authorLove-Gregory, Latisha
dc.contributor.authorGoldenring, James R
dc.contributor.authorKuda, Ondrej
dc.contributor.authorGamazon, Eric R
dc.contributor.authorMills, Jason C
dc.contributor.authorAbumrad, Nada A
dc.contributor.orcidJacome-Sosa, Miriam [0000-0003-3949-3618]
dc.contributor.orcidLo, Hei-Yong G [0000-0001-7253-6873]
dc.contributor.orcidGoldenring, James R [0000-0002-7833-2940]
dc.contributor.orcidKuda, Ondrej [0000-0001-7034-4536]
dc.contributor.orcidGamazon, Eric R [0000-0003-4204-8734]
dc.contributor.orcidAbumrad, Nada A [0000-0002-6475-0877]
dc.date.accessioned2022-01-06T12:55:53Z
dc.date.available2022-01-06T12:55:53Z
dc.date.issued2021-11-02
dc.date.updated2022-01-06T12:55:52Z
dc.description.abstractThe gastric epithelium is often exposed to injurious elements and failure of appropriate healing predisposes to ulcers, hemorrhage, and ultimately cancer. We examined the gastric function of CD36, a protein linked to disease and homeostasis. We used the tamoxifen model of gastric injury in mice null for Cd36 (Cd36-/-), with Cd36 deletion in parietal cells (PC-Cd36-/-) or in endothelial cells (EC-Cd36-/-). CD36 expresses on corpus ECs, on PC basolateral membranes, and in gastrin and ghrelin cells. Stomachs of Cd36-/- mice have altered gland organization and secretion, more fibronectin, and inflammation. Tissue respiration and mitochondrial efficiency are reduced. Phospholipids increased and triglycerides decreased. Mucosal repair after injury is impaired in Cd36-/- and EC-Cd36-/-, not in PC-Cd36-/- mice, and is due to defect of progenitor differentiation to PCs, not of progenitor proliferation or mature PC dysfunction. Relevance to humans is explored in the Vanderbilt BioVu using PrediXcan that links genetically-determined gene expression to clinical phenotypes, which associates low CD36 mRNA with gastritis, gastric ulcer, and gastro-intestinal hemorrhage. A CD36 variant predicted to disrupt an enhancer site associates (p < 10-17) to death from gastro-intestinal hemorrhage in the UK Biobank. The findings support role of CD36 in gastric tissue repair, and its deletion associated with chronic diseases that can predispose to malignancy.
dc.identifier.doi10.17863/CAM.79660
dc.identifier.eissn2399-3642
dc.identifier.issn2399-3642
dc.identifier.otherPMC8563937
dc.identifier.other34728772
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332214
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s42003-021-02765-z
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2399-3642
dc.sourcenlmid: 101719179
dc.subjectAnimals
dc.subjectCD36 Antigens
dc.subjectEndothelial Cells
dc.subjectFemale
dc.subjectGastric Mucosa
dc.subjectGastritis
dc.subjectGastrointestinal Hemorrhage
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectStomach Ulcer
dc.titleCD36 maintains the gastric mucosa and associates with gastric disease.
dc.typeArticle
dcterms.dateAccepted2021-10-06
prism.issueIdentifier1
prism.publicationNameCommun Biol
prism.volume4
pubs.funder-project-idNCRR NIH HHS (S10 RR027552)
pubs.funder-project-idNIA NIH HHS (R56 AG068026)
pubs.funder-project-idNCI NIH HHS (R01 CA239645)
pubs.funder-project-idNIDDK NIH HHS (P30 DK052574, R01 DK060022, R01 DK094989, P30 DK056341, R01 DK105129, R01 DK101332, P30 DK056338, R01 DK048370)
pubs.funder-project-idNHGRI NIH HHS (R01 HG011138)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s42003-021-02765-z

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