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Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen.

ABSTRACT: cDNA clones encoding CD31 have been isolated by transient expression. The sequence of CD31 expressed on human umbilical vein endothelial cells (HUVEC) is identical to that expressed on the monocyte-like cell line HL60. In HUVEC. CD31 is concentrated in regions of cell-cell contacts. CD31 is a member of the Ig superfamily and is most closely related to the carcinoembryonic antigen CEA, consisting of four contiguous C2 domains. The localization of CD31 to regions of cell-cell contacts, and the sequence similarity to CEA, a known intercellular adhesion molecule (ICAM), strongly suggest that CD31 may function as an ICAM, possibly mediating endothelial cell-cell contacts and also promoting interactions between leukocytes and endothelial cells.

SUBMITTER: Simmons DL

PROVIDER: S-EPMC2187965 | biostudies-other | 1990 Jun

REPOSITORIES: biostudies-other

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Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen.

Simmons D L DL Walker C C Power C C Pigott R R

The Journal of experimental medicine 19900601 6

cDNA clones encoding CD31 have been isolated by transient expression. The sequence of CD31 expressed on human umbilical vein endothelial cells (HUVEC) is identical to that expressed on the monocyte-like cell line HL60. In HUVEC. CD31 is concentrated in regions of cell-cell contacts. CD31 is a member of the Ig superfamily and is most closely related to the carcinoembryonic antigen CEA, consisting of four contiguous C2 domains. The localization of CD31 to regions of cell-cell contacts, and the seq ...[more]

PMID: 2351935

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Project description:Patients with nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) commonly develop atherosclerosis through a mechanism that is not well delineated. These diseases are associated with steatosis, inflammation, oxidative stress, and fibrosis. The role of insulin resistance in their pathogenesis remains controversial. Albumin (Alb)Cre+ Cc1flox ( fl ) /fl mice with the liver-specific null deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1; alias Cc1) gene display hyperinsulinemia resulting from impaired insulin clearance followed by hepatic insulin resistance, elevated de novo lipogenesis, and ultimately visceral obesity and systemic insulin resistance. We therefore tested whether this mutation causes NAFLD/NASH and atherosclerosis. To this end, mice were propagated on a low-density lipoprotein receptor (Ldlr) -/- background and at 4 months of age were fed a high-cholesterol diet for 2 months. We then assessed the biochemical and histopathologic changes in liver and aortae. Ldlr-/-AlbCre+Cc1fl/fl mice developed chronic hyperinsulinemia with proatherogenic hypercholesterolemia, a robust proinflammatory state associated with visceral obesity, elevated oxidative stress (reduced NO production), and an increase in plasma and tissue endothelin-1 levels. In parallel, they developed NASH (steatohepatitis, apoptosis, and fibrosis) and atherosclerotic plaque lesions. Mechanistically, hyperinsulinemia caused down-regulation of the insulin receptor followed by inactivation of the insulin receptor substrate 1-protein kinase B-endothelial NO synthase pathway in aortae, lowering the NO level. This also limited CEACAM1 phosphorylation and its sequestration of Shc-transforming protein (Shc), activating the Shc-mitogen-activated protein kinase-nuclear factor kappa B pathway and stimulating endothelin-1 production. Thus, in the presence of proatherogenic dyslipidemia, hyperinsulinemia and hepatic insulin resistance driven by liver-specific deletion of Ceacam1 caused metabolic and vascular alterations reminiscent of NASH and atherosclerosis. Conclusion: Altered CEACAM1-dependent hepatic insulin clearance pathways constitute a molecular link between NASH and atherosclerosis.

Dataset Information

Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen.

Publications

Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen.

Similar Datasets

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