J Korean Diabetes Assoc.  2003 Aug;27(4):323-331.

Effect and Mechanism of High Glucose Level on the Expression of an Adhesion Protein, beta ig-h3, and Cellular Function in Endothelial Cells

• Ha SW
• Yeo HJ
• Bae JS
• Chung SC
• Kim JG
• Kim IS
• Lee IK
• Kim BW

Abstract

BACKGROUND: Diabetes mellitus is a high risk condition for the development of atherosclerotic and thromboembolic macroangiopathy. There are many factors which are involved in development of these processes. Given the central pathogenic role of endotheliopathy in atherosclerosis, it is likely that this vascular monolayer is the ultimate target of injury in response to many cytokines and growth factors. A dysfunctional endothelium may contribute to the proatherogenic environment. Transforming growth factor (TGF-beta) is a key factor in the development of diabetic angiopathy and atherosclerosis because of its effect on the accumulation of extracellular matrix proteins and endothelial function. The adhesive molecule betaig-h3 is an extracellular matrix protein whose expression is induced by TGF-beta. Considering that TGF-beta plays an important role in diabetic complications and that betaig-h3 is a downstream target gene of TGF-beta, we hypothesized that betaig-h3 may also play a role in the development of diabetic angiopathy through its effect on the endothelial function. Therefore, we examined the effects of high glucose level on the expression of betaig-h3 and endothelial function in human umbilical vein endothelial cells (HUVECs). We also studied the mechanisms of this high glucose-induced betaig-h3 expression.
METHODS
Endothelial cells were isolated from human umbilical cord and conditioned with different concentrations of TGF-beta or glucose. We measured TGF-beta and betaig-h3 protein presence/concentration/expression in cell supernatant by ELISA and examined whether TGF-beta is involved in high glucose-induced betaig-h3 expression. Finally, we investigated the biologic function of betaig-h3 in endothelial cells by using adhesion assay.
RESULTS
Our study demonstrated that both high glucose level and TGF-beta induced betaig-h3 protein expression in HUVECs. High glucose level also induced TGF-beta protein expression in cells. Anti-TGF-beta antibody almost completely blocked high glucose-induced betaig-h3 expression. betaig-h3 was found to support the adhesion of endothelial cells.
CONCLUSION
These results suggest that high glucose level upregulates betaig-h3 protein levels through the induction of TGF-beta and that betaig-h3 may play an important role in diabetic angiopathy by regulating adhesive function of endothelial cells.

Keyword

Diabetic angiopathy; Adhesion; High glucose; TGF-beta; betaig-h3; Endothelial cells

MeSH Terms

Adhesives
Atherosclerosis
Cytokines
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endothelial Cells*
Endothelium
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix
Extracellular Matrix Proteins
Glucose*
Human Umbilical Vein Endothelial Cells
Humans
Intercellular Signaling Peptides and Proteins
Transforming Growth Factor beta
Transforming Growth Factors
Umbilical Cord
Adhesives
Cytokines
Extracellular Matrix Proteins
Glucose
Intercellular Signaling Peptides and Proteins
Transforming Growth Factor beta
Transforming Growth Factors