From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy - PubMed (original) (raw)
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From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy
Ying Qian et al. Diabetes. 2008 Jun.
No abstract available
Figures
FIG. 1
Simplified, “classic” model of the pathogenesis of glomerulosclerosis. High extracellular glucose leads to increased mesangial cell glucose uptake via enhanced expression of the facilitative glucose transporter GLUT1, activating metabolic pathways that result in increased ROS and AGE generation, which in turn activate a number of signaling pathways that augment ECM production directly via protein kinase Cβ stimulation of AP-1 transcriptional activation, ERK pathways, and, critically, TGF-β1 synthesis, which in an autocrine and paracrine fashion stimulates its signaling pathways to further enhance ECM protein synthesis. Ang II, angiotensin II; DAG, diacylglycerol; PKC, protein kinase C; ROS, reactive oxidant species.
References
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- Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol. 2003;23:532–543. - PubMed
- Heilig CW, Liu Y, England RL, Freytag SO, Gilbert JD, Heilig KO, Zhu M. Concepcion LA, Brosius FC 3rd: D-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I–sensitive glucose uptake in rat mesangial cells: implications for diabetic nephropathy. Diabetes. 1997;46:1030–1039. - PubMed
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