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)

We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a 3'-directed regional cDNA library from cultured human mesangial cells. Megsin is a novel serine protease inhibitor (serpin), and the level of megsin RNA/protein expression is up-regulated in patients with IgA nephropathy or diabetic nephropathy, suggesting a link between megsin expression and the pathogenesis of mesangial expansion and/or proliferation. To assess the pathophysiological significance of megsin, we produced human megsin transgenic mice. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells.
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PMID:Mesangial cell-predominant gene, megsin. 1238 81

Diabetic nephropathy is the most common cause of end-stage renal failure. The primary glomerular changes in diabetic nephropathy are diffuse and nodular glomerulosclerosis, manifested by an increase in mesangial matrix. Research has demonstrated that advanced glycation end products (AGEs), oxidative stress, and carbonyl stress might play a crucial role in the pathogenesis of diabetic nephropathy via multiple mechanisms. AGEs augment extracellular matrix synthesis, contribute to the release of proinflammatory cytokines and expression of growth factors and adhesion molecules, and interact with the renin-angiotensin system. Megsin is a novel serine protease inhibitor predominantly expressed in mesanguim. Megsin is upregulated in kidney samples of patients with diabetic nephropathy. Transgenic mice overexpressing megsin spontaneously develop kidney disease characterized by mesangial injury. Megsin is likely to contribute to mesangial injury in the process of diabetic nephropathy. Lack of appropriate animal models has hampered understanding the pathogenesis of diabetic nephropathy and development of effective therapies. Megsin and AGEs are suitable targets for new drugs of diabetic nephropathy and for the development of appropriate animal models of diabetic nephropathy.
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PMID:Synergistic contributions of carbonyl stress and megsin in diabetic nephropathy. 1603 83