Effect of high glucose on synthesis and gene expression of collagen and fibronectin in cultured vascular smooth muscle cells

Abstract

Diabetes mellitus is an important risk factor of atherosclerosis. Although the mechanism for accelerated atherosclerotic disease in diabetes mellitus is not clear, extracellular matrix formation by vascular smooth muscle cells has been accepted to play 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, implicating high glucose for the development of diabetic nephropathy. We studied here the effect of high glucose on the synthesis and gene expression of collagen and fibronectin in vascular smooth muscle cells. We found that vascular smooth muscle cells grown in high glucose (25 mM) medium for 1, 2, and 3 days synthesized more collagen and noncollagen protein, as compared to the cells grown in normal glucose (5.5 mM) medium for the same periods of time. We also found that cells grown in high glucose for 1, 2, and 3 days expressed higher level of type 1 procollagen mRNA than that of the cells grown in normal glucose. There was, however, no difference in the amount of newly synthesized fibronectin between cells grown in normal and high glucose condition. These results suggest hyperglycemic condition in diabetes may accelerate the atherosclerotic process by stimu-lating vascular smooth muscle cells to produce more collagen. K e y w o r d s : vascular smooth muscle cell, collagen, fibronectin, high glucose, diabetes mellitus, atherosclerosis

TGF‐β‐induced protein βig‐h3 is upregulated by high glucose in vascular smooth muscle cells

“…In addition, the high glucoseinduced big-h3 production appears to be mediated by TGF-b because TGF-b production is also increased by high glucose and an anti-TGF-b antibody almost completely blocks the big-h3 production induced by high glucose. There have been a variety of studies reporting that high glucose per se would be an important contributing factor to the development of diabetic complications, such as diabetic nephropathy and atherosclerosis [Ayo et al, 1990;Ziyadeh et al, 1994;Spiro et al, 1995;Ha et al, 1997;King and Wakasaki, 1999]. It is well known that high glucose can stimulate TGF-b expression in mesangial cells and proximal tubular epithelial cells, which, in turn, stimulates the production of extracellular matrix [Ziyadeh et al, 1990[Ziyadeh et al, , 1994.…”

“…Hyperglycemia has been suggested to affect the synthesis of extracellular matrix proteins by vascular smooth muscle cells (VSMCs) [Schwartz et al, 1992;Ross, 1993;Ha et al, 1997]. There have also been many reports demonstrating that high glucose stimulates extracellular matrix synthesis in cultured mesangial cells by stimulating TGF-b expression [Ayo et al, 1990;Studer et al, 1993;Ziyadeh et al, 1994].…”

Glucolipotoxicity: A Proposed Etiology for Wooden Breast and Related Myopathies in Commercial Broiler Chickens

“…Upregulation of the polyol pathway, specifically its first step, in wooden breast and white striping is supported by an accumulation of sorbitol in the pectoralis major (Abasht et al, 2016;Boerboom et al, 2018). One notable effect of polyol pathway stimulation is the induction of collagen synthesis (Bleyer et al, 1994;Ha et al, 1997) due at least in part to transcriptional activation of transforming growth factor-β (TGFβ) (Ishii et al, 1998;Han et al, 1999;Tokudome et al, 2004). All three isoforms of TGF-β are considered important regulators of inflammation, extracellular matrix protein deposition, and fibrosis, and altered activity of TGF-β proteins is known to contribute to various fibroproliferative disorders in humans (Pohlers et al, 2009).…”

Association of type III collagen turnover with cardiovascular outcomes and impact with canagliflozin in the CANVAS Program: A post hoc analysis

“…34,35 In another study, aortic smooth muscle cells cultured in high glucose media expressed increased COL I and III levels compared with cells cultured in normal glucose media. 36,37 The lowering of glucose by CANA may therefore reduce COL III formation.…”