CD36 maintains the gastric mucosa and associates with gastric disease

Abstract

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.

Gastroduodenal injury and repair: novel targets for therapeutic intervention

“…In the stomach, CD36 localized to endothelial and parietal cells, where it was shown to regulate lipid metabolism [36 ▪▪ ]. Interestingly, deletion of CD36 in endothelial, but not parietal cells, impeded the recovery of parietal cell number after injury by blocking the development of parietal cell progenitors [36 ▪▪ ]. This work linked lipid metabolism to gastric repair after injury, which is a novel concept and another target for therapeutic intervention.…”

“…Although great attention is paid to the role of chief cells in SPEM metaplasia, once a deep injury occurs, it is unclear how parietal cells repopulate the mucosa. New work in the past year suggests a strong association of CD36 (CD36 molecule), the effector in small intestine required for the optimal secretion of chylomicrons and mucosal repair after acute parietal cell loss in stomach [36 ▪▪ ]. In the stomach, CD36 localized to endothelial and parietal cells, where it was shown to regulate lipid metabolism [36 ▪▪ ].…”

“…New work in the past year suggests a strong association of CD36 (CD36 molecule), the effector in small intestine required for the optimal secretion of chylomicrons and mucosal repair after acute parietal cell loss in stomach [36 ▪▪ ]. In the stomach, CD36 localized to endothelial and parietal cells, where it was shown to regulate lipid metabolism [36 ▪▪ ]. Interestingly, deletion of CD36 in endothelial, but not parietal cells, impeded the recovery of parietal cell number after injury by blocking the development of parietal cell progenitors [36 ▪▪ ].…”

The Role of Lipid Metabolism in Gastric Cancer

“…Other symptoms could be detected (e.g., reduced tissue respiration and mitochondrial efficiency, phospholipids increasing, as well as triglycerides decreasing). CD36 and its absence have been found to act in chronic diseases predisposing to malignancy ( 101 ).…”

Endothelial stiffening induced by CD36-mediated lipid uptake leads to endothelial barrier disruption and contributes to atherosclerotic lesions

“…Indeed, global loss of CD36 results in a decreased uptake of FAs in multiple tissues including adipose 20,21 . Furthermore, endothelial-specific loss of CD36 is sufficient to decrease incorporation of triglycerides 18,19 . Here, we establish the role of CD36-mediated uptake of LCFAs in endothelial stiffening and elucidate the signaling basis of this effect.…”