Alteration of Endothelins: A Common Pathogenetic Mechanism in Chronic Diabetic Complications

Chakrabarti, Subrata; Khan, Zia A.; Cukiernik, Mark; Fukuda, Gen; Chen, Shali; Mukherjee, Shankar

doi:10.1080/15604280214939

Cited by 16 publications

(14 citation statements)

References 197 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3][4][5]18 We have previously demonstrated an important role of hyperglycemia-induced ET-1 expression in increased ECM protein deposition. 4,15,18 We have also shown that hyperhexosemia-induced increased FN mRNA expression can be prevented by bosentan treatment in retinas and kidneys of both diabetic and galactose-fed rats.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Furthermore, biochemical anomalies implicated in hyperglycemia-induced vascular dysfunction such as, nonenzymatic glycation, oxidative stress, and alteration in growth factor and vasoactive factor expression are all involved in alteration of ETs and increased ECM deposition. 1,2,23,24 It is being increasingly realized that all of these hyperglycemiainduced secondary factors share the capacity to activate MAPKs. These studies suggest that MAPK activation may represent a common signal transduction of glucose-induced ET-1 mediated ECM protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…25 On the other hand, ET-1 receptor, being G q coupled, may activate phospholipase C, increase intracellular calcium and may cause PKC activation. 1,2,26 Hyperglycemia-induced NF-kB activation may also cause upregulation of ET-1. 27 In several systems, ET-1 has been also shown to mediate its effect via MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

“…6,8 Elaboration of various hyperglycemia-induced vasoactive factors and growth factors is implicated in augmented FN expression. 1,2 Mechanisms of increased ECM protein production may also include activation of mitogen-activated protein kinase (MAPK) pathway. 8 MAP kinase family form a group of serine/threonine kinases that are activated via phosphorylation following stimulation.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Extracellular signal-regulated kinase (ERK) in glucose-induced and endothelin-mediated fibronectin synthesis

Xin

Khan

Chen

et al. 2004

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Increased extracellular matrix protein deposition and basement membrane thickening are important features of diabetic angiopathy. One key matrix protein that has been shown to be instrumental in basement membrane thickening is fibronectin (FN). We have previously demonstrated that glucose-induced increased expression of endothelin-1 (ET-1), may in part, be responsible for increased FN expression via nuclear factor-jB (NF-jB) and activating protein (AP-1) activation. The present study was aimed at elucidating the mechanism of ET-1 with respect to mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation and glucose-induced FN upregulation. Human endothelial cells were exposed to either low (5 mM) or high (25 mM) glucose levels. Cells in low glucose were also treated with ET-1 peptide (5 nM). In addition, we treated cells exposed to high glucose levels with specific MAPK/ERK inhibitor PD098059 (50 lM), dual ETreceptor antagonist, bosentan (10 lM), and PKC blocker, chelerythrine (1 lM). Following incubation period, RNA and total proteins were extracted for RT-PCR for FN and immunoblot analysis of MAPK/ERK activation. Confocal microscopy was performed for analysis of FN protein and nuclear localization of activated Elk. Electrophoretic mobility shift assay was carried out to detect NF-jB and AP-1 activation. Our data demonstrates that high glucose-induced upregulation of FN messenger RNA and protein levels occur via activation of MAPK/ ERK pathway, which was prevented by treatment of cells with bosentan, PD098059 and PKC blocker chelerythrine. Confocal microscopy demonstrated nuclear localization of phospho-Elk protein. Glucoseinduced FN expression was also associated with protein kinase C, NF-jB, and AP-1 activation. These results suggested that glucose-induced, ET-and PKC-dependent, upregulation of FN is, in part, mediated via MAPK/ ERK activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Extracellular signal-regulated kinase (ERK) in glucose-induced and endothelin-mediated fibronectin synthesis

Xin

Khan

Chen

et al. 2004

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Circulating ET-1 concentrations are increased in most cardiovascular diseases (CVDs), playing a critical role in the structural and functional alterations associated with the development of diabetic vascular complications and hypertension (9). ET-1 is also elevated in atherosclerotic plaques and promotes the expression of inflammatory genes in VSMCs (8).…”

mentioning

confidence: 99%

Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

et al. 2015

View full text Add to dashboard Cite

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of endothelin-1 and activation of CREB. Infusion of GIP increases plasma OPN concentrations in healthy individuals. Plasma endothelin-1 and OPN concentrations are positively correlated in patients with critical limb ischemia. Fasting GIP concentrations are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared with control subjects. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients, and expression associates with parameters that are characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration, and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from humans, mice, rats, and pigs, remarkable upregulation is observed in endothelial and smooth muscle cells upon culture conditions, yielding a “vascular disease–like” phenotype. Moreover, the common variant rs10423928 in the GIPR gene is associated with increased risk of stroke in patients with type 2 diabetes.

show abstract

Genotoxic stress and activation of novel DNA repair enzymes in human endothelial cells and in the retinas and kidneys of streptozotocin diabetic rats

Wang

George

Chen

et al. 2012

Diabetes Metabolism Res

Self Cite

View full text Add to dashboard Cite

show abstract

Alteration of Endothelins: A Common Pathogenetic Mechanism in Chronic Diabetic Complications

Cited by 16 publications

References 197 publications

Extracellular signal-regulated kinase (ERK) in glucose-induced and endothelin-mediated fibronectin synthesis

Extracellular signal-regulated kinase (ERK) in glucose-induced and endothelin-mediated fibronectin synthesis

Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

Genotoxic stress and activation of novel DNA repair enzymes in human endothelial cells and in the retinas and kidneys of streptozotocin diabetic rats

Contact Info

Product

Resources

About