- Effect and Mechanism of High Glucose Level on the Expression of an Adhesion Protein, beta ig-h3, and Cellular Function in Endothelial Cells.
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Sung Woo Ha, Hye Jin Yeo, Jong Sup Bae, Sung Chang Chung, Jung Guk Kim, In San Kim, In Kyu Lee, Bo Wan Kim
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Korean Diabetes J. 2003;27(4):323-331. Published online August 1, 2003
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- 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.
- Effect of Transforming Growth Factor-Induced Gene Product, beta ig-h3 on Proliferation, Migration, and Adhesion of Aortic Smooth Muscle Cells Cultured in High Glucose.
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Sung Woo Ha, Gui Hwa Jung, He Jin Yeo, Jong Sup Bae, Soon Hee Lee, Jung Guk Kim, Rang Woon Park, In San Kim, Bo Wan Kim
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Korean Diabetes J. 2002;26(4):286-295. Published online August 1, 2002
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Abstract
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- BACKGROUND
Diabetes mellitus is associated with a substantial increase in the prevalence of atherosclerotic disease. There are many factors which are involved in development of these processes. Transforming growth factor (TGF-beta) is known to be an important factor in the pathogenesis of diabetic vascular complications. TGF-beta-induced gene-h3 (beta ig-h3) is an adhesive molecule whose expression is induced by TGF-beta. Considering that TGF-beta plays an important role in diabetic complications and that beta ig-h3 is induced by TGF-beta, we hypothesized that beta ig-h3 may also play a role in the development of diabetic angiopathy. Then, we examined the effects of beta ig-h3 on biologic function of vascular smooth muscle cells (VSMCs) and potential roles of beta ig-h3 in the pathognesis of diabetic angiopathy. METHODS: VSMCs were isolated from rat thoracic aorta. We conditioned cells with different concentration of TGF-beta or glucose. We measured TGF-beta and beta ig-h3 protein in cell supernatant by ELISA. We also examined whether TGF-beta involves in high glucose-induced beta ig-h3 expression. Finally, we did proliferation, migration, and adhesion assay to investigate biologic function of beta ig-h3 in VSMCs. RESULTS: Our results demonstrated that TGF-beta induced beta ig-h3 expression in VSMCs in dose dependent manners. High glucose induced TGF expression as well as beta ig-h3 protein. Finally, beta ig-h3 was found to support the proliferation, migration, and adhesion of rat VSMCs. CONCLUSION: These results suggest that high glucose-and TGF-beta-induced beta ig-h3 may play an important role in diabetic angiopathy by regulating proliferation, migration, and adhesion of VSMCs.
- Effect of Transforming Growth Factor-B1 and Platelet Derived Growth Factor on Synthesis and Gene Expression of Collagen and Non-Collagen Protein in Aortic Smooth Muscle Cells Cultured in Different Concentrations of Insulin and Glucose.
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Kun Young Sohn, In San Kim, Bo Wan Kim, Jung Guk Kim, Sung Woo Ha, Jick Hwa Nam, Seong Mo Koo, Rang Woon Park, Sam Kweon
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Korean Diabetes J. 1999;23(4):518-529. Published online January 1, 2001
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Abstract
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- BACKGROUND
The mechanism for accelerated atberosclerosis in diabetes mellitus is unclear although diabetes mellitus is associated with substantial increase in prevalence of atherosclerotic disease. Extracellular matrix formation by vascular smooth muscle cells has been accepted as playing important roles during development of atherosclerosis. High glucose condition has been reported to increase the synthesis of extracellular matrix such as collagen and fibronectin in cultured mesangial cells. Insulin and some cytokines such as TGF-B and PGF have also been reported to stimulate the synthesis of collagen in mesangial cells. So we studied the effect of high glucose, insulin, TGF-Band PDGF on vascular smooth muscle cells. METHODS: To determine the effect of bigh glucose condition on collagen synthesis in vascular smooth muscle cells, cells were grown in the culture medium containing either normal (5.5 mM) or high (25 mM) glucose. And we used several concentrations of TGF-B1PDGF-BB and insulin in order to determine the synergistic effects of collagen synthesis and type I collagen mRNA expression. RESULTS: We observed that cells cultured in high glucose media synthesized more collagen and increased expression of type I collagen mRNA as compared to normoglycemic media. The amount of synthesized collagen and type I collagen mRNA expression increased proportionally to the increase in insulin concentration. There was no relationship of TGF-B1or PDGF-BB with the expression of type I collagen mRNA but these cytokines stimulated the synthesis of collagen and noncollagen protein. There was no synergistic effect of col)agen synthesis and type 1collagen mRNA expression by high glucose, insulin, and cytokines. CONCLUSION: These results suggest that TGF-Band PDGF may not influence type I collagen mRNA expression under hyperglycemia or hyperinsulinemia in vascular smooth muscle cells. Further studies about the other types of collagen expressions such as type IV, and V are needed because TGF-Band PDGF stimulated the synthesis of collagen and noncollagen protein.
- Effects of insulin and insulin-like growth factor-1 on collagen and fibronectin synthesis in endothelial cells and fibroblasts.
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In Kyu Lee, Byung Chae Jo, Kun Young Sohn, Rang Woon Park, In San Kim
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Korean Diabetes J. 1993;17(4):351-358. Published online January 1, 2001
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- No abstract available.
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