Role of PKC and TGF-β Receptor in Glucose-Induced Proliferation of Smooth Muscle Cells

Yasuda, Yutaka; Nakamura, Jiro; Hamada, Yoji; Nakayama, Mikihiro; Chaya, Sadao; Naruse, Keiko; Nakashima, Eitaro; Kato, Koichi; Kawanishi, Hideki; Hotta, Nigishi

doi:10.1006/bbrc.2001.4310

Cited by 29 publications

(20 citation statements)

References 45 publications

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“…Additionally, inhibition of aldose reductase, by promoting HNE accumulation, could inhibit mitogenic signaling pathways activated by glucose. It has been shown that inhibition of aldose reductase prevents hyperglycemia-induced (14,15,44) and growth factor-induced (17) PKC activation, which is essential for SMC growth in high glucose (45). Regardless of the mechanism, because aldose reductase inhibitors prevent intimal expansion (this study) as well as inflammation associated with nuclear factor-B activation (16,17,46), without drastically decreasing lesion cellularity (Fig.…”

Section: Discussionmentioning

confidence: 61%

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

et al. 2006

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Section: Discussionmentioning

confidence: 61%

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

et al. 2006

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“…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. Recently, it was reported that high glucose did not increase the amount of active and total TGF-b in the conditioned media of VSMCs [Yasuda et al, 2001], although it was reported that the proliferation of VSMCs was significantly accelerated under high glucose conditions and that the anti-TGF-b antibody inhibited this increase. Although they could not detect increased TGF-b production, they suggested that high glucose-induced cell proliferation could be mediated by TGF-b.…”

Section: Discussionmentioning

confidence: 99%

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

Bae

Yeo

et al. 2002

J of Cellular Biochemistry

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TGF-beta-induced gene-h3 (beta ig-h3) is an adhesive molecule that interacts with integrins. Because TGF-beta plays an important role in diabetic complications and beta ig-h3 serves as a cell substrate, we hypothesized that diabetic conditions might increase beta ig-h3 synthesis in vascular smooth muscle cells (VSMCs), which may subsequently contribute to the pathogenesis of diabetic angiopathy. The concentrations of beta ig-h3 and TGF-beta were measured in conditioned media using an enzyme-linked immunosorbent assay. An immunohistochemical study showed that beta ig-h3 was expressed in the VSMCs and the matrix of rat aortas. TGF-beta stimulated beta ig-h3 production, and high glucose induced beta ig-h3 as well as TGF-beta production in the VSMCs. The high glucose-induced beta ig-h3 expression was almost entirely blocked by an anti-TGF-beta antibody. beta ig-h3 protein mediated the adhesion, spreading, migration, and proliferation of rat VSMCs. These results suggest that the high glucose-induced beta ig-h3 in VSMCs regulates VSMC functions and may play an important role in diabetic angiopathy.

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“…31 Recently published data have also shown a stimulating effect of high glucose concentrations on cellular proliferation of vascular smooth muscle cells, suggesting that transforming growth factor-␤ and protein kinase C (PKC) play an important role in this process. 32 It seems possible that glucose, by activation of PKC, enhances the expression of c-fos and c-jun, which as components of the activator protein-1 (AP-1) complex are known to interact with the AP-1 binding site on the transforming growth factor-␤ receptor type II promotor. 33 Apart from the potential role of paracrine factors, the experimental design may contribute to alternative results.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone and d -Glucose Stimulate the Proliferation of Human Cardiac Myofibroblasts In Vitro

et al. 2002

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Abstract-The renin-angiotensin-aldosterone-system appears to be involved in the development of cardiac fibrosis in rodents, characterized by nonepithelial cell proliferation and changes in the extracellular matrix. The aim of our study was to investigate the effect of high aldosterone concentrations on the proliferation of human cardiac interstitial cells in vitro. In addition, the effect of D-glucose as another risk factor for fibrosis, eg, in the diabetic heart, was investigated. Human cardiac myofibroblast cultures were established, and growth rates were measured by WST-1 assay in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). Cells in culture showed a significant increase in number between 24 to 72 hours of cultivation under basal conditions (DMEM, 10% fetal calf serum). Aldosterone at high concentrations (10 Ϫ8 and 10 Ϫ7 mol/L) significantly (PϽ0.01) increased the proliferation of cultured cardiac myofibroblasts. Comparable effects were observed after incubation of the cells with high D-glucose concentrations (15 and 25 mmol/L, PϽ0.01). No additive growth stimulation was evident when the cells were incubated in medium containing both aldosterone and D -glucose. These results suggest a role for aldosterone and glucose in mediating the cardiac fibrosis through stimulation of myofibroblast growth in patients with dysregulated renin-angiotensin-aldosterone-system (especially hyperaldosteronism) and impaired glucose homeostasis. R ecent clinical studies demonstrate a reduction in cardiovascular mortality in patients with heart failure treated with ACE inhibitors, angiotensin II blockers, and aldosterone antagonists. These effects were also seen in patients with diabetes mellitus. Ramipril reduced not only cardiac failure and myocardial infarction but also diabetic complications and the incidence of new manifestations of diabetic disease. 1 In the RALES trial (Randomized Aldactone Evaluation Study), spironolactone added to standard therapy (ACE inhibitors, loop diuretics, digoxin, etc) had a beneficial effect on mortality in patients with congestive heart failure, with a 30% reduction in mortality seen in the spironolactone group. 2 This effect was only significant in patients with elevated serum levels of collagen synthesis markers, suggesting limitation of excessive extracellular matrix turnover as one mechanism contributing to the beneficial effect of spironolactone. 2

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Role of PKC and TGF-β Receptor in Glucose-Induced Proliferation of Smooth Muscle Cells

Cited by 29 publications

References 45 publications

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

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

Aldosterone and d -Glucose Stimulate the Proliferation of Human Cardiac Myofibroblasts In Vitro

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