High glucose attenuates insulin-induced VEGF expression in bovine retinal microvascular endothelial cells

Wu, Hao; Xia, Xin; Jiang, Chunhui; Wu, Jianfeng; Zhang, S; Zheng, Zhi; Liu, W; Zhang, Y; Ren, Hui; Wei, Chunsheng; Xu, Xiaoyin

doi:10.1038/eye.2009.157

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…In this study we have seen VEGF upregulation after 48 hrs. This is in keeping with studies in endothelial cells from other sources [9, 46]. Some studies have demonstrated VEGF upregulation following a short period of glucose exposure.…”

Section: Discussionsupporting

confidence: 89%

ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy

Zuo²,

Chakrabarti³

et al. 2010

Journal of Ophthalmology

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Diabetic retinopathy is one of the most common causes of blindness in North America. Several signaling mechanisms are activated secondary to hyperglycemia in diabetes, leading to activation of vasoactive factors. We investigated a novel pathway, namely extracellular signal regulated kinase 5 (ERK5) mediated signaling, in modulating glucose-induced vascular endothelial growth factor (VEGF) expression. Human microvascular endothelial cells (HMVEC) were exposed to glucose. In parallel, retinal tissues from streptozotocin-induced diabetic rats were examined after 4 months of follow-up. In HMVECs, glucose caused initial activation followed by deactivation of ERK5 and its downstream mediators myocyte enhancing factor 2C (MEF2C) and Kruppel-like factor 2 (KLF2) mRNA expression. ERK5 inactivation further led to augmented VEGF mRNA expression. Furthermore, siRNA mediated ERK5 gene knockdown suppressed MEF2C and KLF2 expression and increased VEGF expression and angiogenesis. On the other hand, constitutively active MEK5, an activator of ERK5, increased ERK5 activation and ERK5 and KLF2 mRNA expression and attenuated basal- and glucose-induced VEGF mRNA expression. In the retina of diabetic rats, depletion of ERK5, KLF2 and upregulation of VEGF mRNA were demonstrated. These results indicated that ERK5 depletion contributes to glucose induced increased VEGF production and angiogenesis. Hence, ERK5 may be a putative therapeutic target to modulate VEGF expression in diabetic retinopathy.

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Section: Discussionsupporting

confidence: 89%

ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy

Zuo²,

Chakrabarti³

et al. 2010

Journal of Ophthalmology

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“…Literature shows that short-time incubations with high glucose increase VEGF synthesis and secretion in glomerular podocytes [13], in mesangial cells [14,15] and in the retinal endothelial cells [16,17] thus, results we obtained in VSMC are in keeping with those obtained in other cell types.…”

Section: Discussionsupporting

confidence: 88%

“…As it is well known, the main feature characterizing diabetes mellitus is hyperglycemia, which plays a pivotal role in the pathogenesis of diabetes vascular complications [12]: hyperglycemia, in particular, modifies VEGF synthesis and secretion in different cell types, such as glomerular podocytes [13], mesangial cells [14,15] and the retinal endothelial cells [16,17]. Only two studies addressed so far the high glucose modulation of VEGF in VSMC: both of them investigated the influence of incubation with high glucose (25 mM) for several VSMC passages in culture [18,19].…”

Section: Introductionmentioning

confidence: 99%

Effects of High Glucose on Vascular Endothelial Growth Factor Synthesis and Secretion in Aortic Vascular Smooth Muscle Cells from Obese and Lean Zucker Rats

Doronzo

Viretto

Russo

et al. 2012

IJMS

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Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed at evaluating the role of high glucose on VEGF-A164 synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with d-glucose (5.5, 15 and 25 mM) or with the osmotic controls l-glucose and mannitol, we measured VEGF-A164 synthesis (western, blotting) and secretion (western blotting and ELISA). We observed that: (i) d-glucose dose-dependently increases VEGF-A164 synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002–0.0001); (ii) all the effects of 15 and 25 mM d-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001); (iii) l-glucose and mannitol reproduce the VEGF-A164 modulation induced by d-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.

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“…BRECs were isolated by homogenization and by a series of filtration steps as described previously [27], and were subsequently cultured in Dulbecco's modified Eagle's medium (DMEM, GIBCO) supplemented with 10% FBS (GIBCO), 100 mg/l heparin (Sigma), 10 mmol/l HEPES (GIBCO), and 15 mg/LECGS (Sigma). The culture plate was coated with Gelatin (Sigma) beforehand.…”

Section: Cell Culturementioning

confidence: 99%