Antioxidant inhibition of protein kinase C—signaled increases in transforming growth factor-beta in mesangial cells

Role of Reactive Oxygen Species in TGF-β1-Induced Mitogen-Activated Protein Kinase Activation and Epithelial-Mesenchymal Transition in Renal Tubular Epithelial Cells

“…We (40) and others (41) have previously demonstrated that H 2 O 2 upregulates TGF-␤1 mRNA and protein expression in glomerular mesangial cells and that antioxidants effectively inhibit high glucose-induced TGF-␤1 expression in mesangial cells (42) and diabetic kidneys (43). These observations together with the finding of this study that TGF-␤1 induces generation In this study, we found that antioxidants effectively reversed TGF-␤1-induced phosphorylation of Smad 2 and MAPK and the changes in E-cadherin and ␣-SMA expression.…”

Comparative Trial of N-Acetyl-Cysteine, Taurine, and Oxerutin on Skin and Kidney Damage in Long-Term Experimental Diabetes

“…Indeed, NAC has been shown to inhibit ROS-induced mesangial apoptosis (34) and to be able to protect cells from glucose-induced inhibition of proliferation (35). Moreover, NAC has been seen to inhibit transforming growth factor-␤ (TGF-␤)-related pathways involved in collagen deposition (36). More recently, NAC proved capable of counteracting the high-glucose-dependent activation of mitogen-activated protein kinase pathways, which are probably involved in the development of microvascular complications of diabetes (37).…”

Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease

“…Hyperglycaemia-induced activation of PKC and diacylglycerol (DAG) has been suggested to be an important mechanism in the endothelial dysfunction and long-term vascular complications in diabetes [107]. Based on in vitro experiments, it has been proposed that PKC activation in glomerular cells induced by high glucose concentrations is followed by increased TGF-b activity [108] and mitogen-activated protein (MAP) kinase activity [109]. In a recent study, treating mesangial cells exposed to high glucose concentrations with antioxidant alfa-tocopherol blocked the increase in PKC, TGF-b and matrix accumulation but did not alter the effect of TGF-b-induced matrix production [108].…”

“…Based on in vitro experiments, it has been proposed that PKC activation in glomerular cells induced by high glucose concentrations is followed by increased TGF-b activity [108] and mitogen-activated protein (MAP) kinase activity [109]. In a recent study, treating mesangial cells exposed to high glucose concentrations with antioxidant alfa-tocopherol blocked the increase in PKC, TGF-b and matrix accumulation but did not alter the effect of TGF-b-induced matrix production [108]. In vivo experiments in which a specific PKCb isoform inhibitor (LY 333 531) was given to STZ-diabetic rats for 3 months the diabetes-associated increase in glomerular TGF-b1 mRNA, matrix accumulation and vascular dysfunctions [i.e.…”