Sequential effects of high glucose on mesangial cell transforming growth factor-β1 and fibronectin synthesis

Oh, Jong Hoon; Ha, Hunjoo; Yu, Mi Ra; Lee, Hi Bahl

doi:10.1046/j.1523-1755.1998.00193.x

Cited by 125 publications

(98 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The TGF␤1 increase observed here in the embryonic heart is consistent with results produced in cultured cells and observed in diabetic tissues. Cultured rodent and human mesangial cells exposed to 450 -540 mg/dl glucose demonstrate increased TGF␤1 secretion, bioactivity, and mRNA expression (Wahab et al, 1996;Hoffman et al, 1998;Oh et al, 1998). A similar up-regulation of TGF␤1 is produced in cultured renal tubule cells (Rocco et al, 1992) and mesothelial cells exposed to hyperglycemia (Ha et al, 2001) and in the kidneys of human diabetics (Chen et al, 2001).…”

Section: Discussionmentioning

confidence: 87%

Hyperglycemia‐induced TGFβ and fibronectin expression in embryonic mouse heart

Smoak

2004

Developmental Dynamics

View full text Add to dashboard Cite

Cardiovascular defects are common in diabetic offspring, but their etiology and pathogenesis are poorly understood. Extracellular matrix accumulates in adult tissues in response to hyperglycemia, and transforming growth factor-beta1 (TGF␤1) likely mediates this effect. The objective of this study was to characterize TGF␤ expression in the organogenesisstage mouse heart and to evaluate TGF␤ and fibronectin expression in embryonic mouse heart exposed to hyperglycemia. Prominent TGF␤1, and minimal TGF␤2 or TGF␤3, protein expression was demonstrated in embryonic day (E) 9.5-E13.5 hearts. Hyperglycemia for 24 hr produced significantly increased fibronectin, slightly increased TGF␤1, and unchanged TGF␤2 or TGF␤3, by immunohistochemistry. Increased TGF␤1 was demonstrated by enzyme-linked immunosorbent assay in embryonic fluid and isolated hearts after hyperglycemia for 24 hr, but not 48 hr. Hyperglycemia increased fibronectin protein and mRNA expression in embryonic hearts after 24 hr, and pericardial injection of TGF␤1 also increased fibronectin mRNA in the embryonic heart. It is proposed that TGF␤1 and fibronectin may play a role in diabetes-induced cardiac dysmorphogenesis.

show abstract

Section: Discussionmentioning

confidence: 87%

Hyperglycemia‐induced TGFβ and fibronectin expression in embryonic mouse heart

Smoak

2004

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Increases or decreases in the production of TGF-β have been linked to numerous disease states, including atherosclerosis and fibrotic disease of the kidney, liver and lung. TGF-β is reported to be increased by elevated glucose and is a known powerful stimulus of extra cellular matrix production (Chen et al, 2003;Oh et al, 1998). High levels of glucose significantly increase levels of TGF-β1 and lead to fibrosis of these organs (Park et al, 1997;Sharma et al, 1997) and induction of diabetic nephropathy (Pantsulaia 2006).…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

View full text Add to dashboard Cite

The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-β isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/ group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-β1 and TGF-β2 mRNA, but not TGF-β3, was increased at 4 and 12 weeks. In sciatic nerve TGF-β3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-β formed homoand heterodimers, of which β 2 /β 3 , β 1 /β 1 , and β 1 /β 3 were significantly increased, while that of the TGF-β 2 /β 2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-β neutralizing antibody prevents the increase in total TGF-β protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-β2 > β1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-β neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-β isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-β neutralizing antibody. These findings implicate upregulation of TGF-β in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy.

show abstract

“…In these cells, high glucose causes increased expression of the type IV collagen and fibronectin genes, mimicking the in vivo alterations (7)(8)(9)(10). Several metabolic effects of high glucose have been postulated to contribute to its impact on gene expression, including de novo diacylglycerol synthesis and activation of protein kinase C (PKC) (7,11,12), increased activity of the polyol pathway (11), oxidative stress (13), and the formation of advanced glycation products (11).…”

mentioning

confidence: 99%

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

2000

View full text Add to dashboard Cite

Increased flux through the hexosamine biosynthetic pathway is associated with altered gene expression. To investigate the underlying mechanisms, we treated glomerular mesangial cells with glucosamine and studied the regulation of the plasminogen activator inhibitor (PAI)-1 gene. Incubating mesangial cells with 2 mmol/l glucosamine for 4 days resulted in a 3.1 ± 0.4-fold increase in PAI-1 mRNA levels (P < 0.01) and a 33 ± 9-fold increase in the activity of a transiently transfected PAI-1 promoter-luciferase reporter gene (P < 0.01). Cotransfection of an expression vector for a dominant-negative type II TGF-␤ receptor with the PAI-1 promoter-reporter gene did not interfere with this effect of glucosamine. However, mutation of 2 putative Sp1 sites in the PAI-1 promoter, at -76 to -71 and -44 to -39, markedly reduced induction of PAI-1 luciferase activity by glucosamine, from 8.9 ± 1.9-fold to 1.7 ± 0.5-fold (P < 0.01). An electrophoretic mobility shift assay demonstrated that glucosamine increased Sp1 DNA binding by 31 ± 11% (P < 0.05), implying that the effects of glucosamine were explained, in part, by changes in Sp1 DNA binding. High glucose (20 mmol/l) also activated the transiently transfected PAI-1 promoter (2.5 ± 0.4-fold). This effect was diminished by mutation of both the PAI-1 promoter Sp1 sites (1.2 ± 0.3-fold, P < 0.05). In addition, 6-diazo-5-oxo-L-norleucine, a glutamine:fructose-6-phosphateamidotransferase inhibitor, blocked the induction by high glucose (4.7 ± 0.8-to 0.9 ± 0.1-fold, P < 0.01). These results indicate that stimulation of the PAI-1 promoter by both high glucose and glucosamine involves Sp1 and that the hexosamine pathway may be involved in the regulation of gene expression by high glucose in glomerular mesangial cells. Diabetes 49:863-871, 2000

show abstract

Sequential effects of high glucose on mesangial cell transforming growth factor-β1 and fibronectin synthesis

Abstract: The present finding demonstrate that HG stimulates TGF-beta 1 very early and prior to FN production and that HG-induced FN production is mediated by TGF-beta. This finding is consistent with the view that TGF-beta mediates increased ECM accumulation by MC under high glucose conditions.

Cited by 125 publications

References 33 publications

Hyperglycemia‐induced TGFβ and fibronectin expression in embryonic mouse heart

Hyperglycemia‐induced TGFβ and fibronectin expression in embryonic mouse heart

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

Contact Info

Product

Resources

About