TY - JOUR
T1 - CD36 maintains the gastric mucosa and associates with gastric disease
AU - Jacome-Sosa, Miriam
AU - Miao, Zhi Feng
AU - Peche, Vivek S.
AU - Morris, Edward F.
AU - Narendran, Ramkumar
AU - Pietka, Kathryn M.
AU - Samovski, Dmitri
AU - Lo, Hei Yong G.
AU - Pietka, Terri
AU - Varro, Andrea
AU - Love-Gregory, Latisha
AU - Goldenring, James R.
AU - Kuda, Ondrej
AU - Gamazon, Eric R.
AU - Mills, Jason C.
AU - Abumrad, Nada A.
N1 - Funding Information:
We acknowledge assistance of the following facilities at Washington University: Nutrition and Obesity Research Center Cellular and Molecular Biology Core (NORC CMBC, P30 DK056341) with mitochondrial function and cytokine/hormone levels, the Hope Center Animal Surgery Core for pylorus ligation studies, the Hope Center Alafi Neu-roimaging Laboratory (NIH Shared Instrumentation Grant S10-RR-027552) for Nano-zoomer slide scanning and the Advanced Imaging and Tissue Analysis Core (AITAC, P30 DK052574) of the Digestive Disease Research Core Center (DDRC) for histology and microscopy. We acknowledge assistance of Karen Green at the Department of Pathology Electron Microscopy Center. We also acknowledge the Metabolomics Core Facility at the Physiology Institute of the Czech Academy of Sciences for lipidomics profiling. This work was supported by grants from the National Institute of Health DK060022 (NAA), DK060022S1 (MJS), DK094989, DK105129 (JCM), DK48370 and DK101332 (JRG), by NIH//NIA AG068026 and R01HG011138 (ERG) and a grant from Ministry of Education, Youth and Sports of the Czech Republic LTAUSA18104 (OK).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The 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.
AB - The 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.
UR - http://www.scopus.com/inward/record.url?scp=85118426796&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-02765-z
DO - 10.1038/s42003-021-02765-z
M3 - Article
C2 - 34728772
AN - SCOPUS:85118426796
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1247
ER -