Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metalion vanadate has insulin-like effects and has been advocated for use in humans as a therapeutic modality for diabetes mellitus. However, since vanadate is a tyrosine phosphatase inhibitor, it may result in undesirable activation of target cells. We studied the effect of vanadate on human mesangial cells, an important target in diabetic nephropathy. Vanadate stimulated DNA synthesis and PDGF B chain gene expression. Vanadate also inhibited total tyrosine phosphatase activity and stimulated tyrosine phosphorylation of a set of cellular proteins. Two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and herbimycin A, blocked DNA synthesis induced by vanadate. Vanadate also stimulated phospholipase C and protein kinase C. Downregulation of protein kinase C abolished vanadate-induced DNA synthesis. Thus, vanadate-induced mitogenesis is dependent on tyrosine kinases and protein kinase C activation. The most likely mechanism for the effect of vanadate on these diverse processes involves the inhibition of cellular phosphotyrosine phosphatases. These studies demonstrating that vanadate activates mesangial cells may have major implications for the therapeutic potential of vanadate administration in diabetes. Although vanadate exerts beneficial insulin-like effects and potentiates the effect of insulin in sensitive tissue, it may result in undesirable activation of other target cells, such as mesangial cells.
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PMID:Activation of mesangial cells by the phosphatase inhibitor vanadate. Potential implications for diabetic nephropathy. 788 73

Many studies have suggested deleterious effects of platelet-derived growth factor (PDGF) released by intrinsic renal cells during glomerulonephritis (GN). Increase in PDGF B chain expression has particularly been noted in glomeruli of patients with GN. Less known is the role of PDGF A chain both in the normal kidney and renal diseases. Several lines of evidence have indicated the involvement of PDGF-A in renal graft rejection. Furthermore, an increased expression of PDGF-A has also been observed in the course of human diabetic nephropathy. Still, the role of PDGF-A in the development and progression of GN remains unclear.
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PMID:[The role of platelet-derived growth factor A (PDGF-A) in hypertension and renal diseases. Part 2: a role of PDGF-A in kidney diseases]. 1551 44