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

Glomerular basement membrane (GBM) thickening has been reported to be a characteristic change of diabetic nephropathy. Previous studies of GBM in animal models of diabetes indicated that there are no consensus in the alteration of synthesis of GBM component. The aim of this study was to determine whether the glomerular mRNA levels encoding type I and type IV collagen. B1 laminin, and heparan sulfate proteoglycan (HSPG) are altered in streptozotocin diabetic rats with or without insulin therapy. Glomerular mRNA levels for type I and type IV collagen, laminin B1, were significantly increased, but that for HSPG were marked decreased in 4 week diabetic rats compared with age-matched control rats. Insulin therapy has normalized these abnormally regulated gene expressions. Renal morphology shows no significant changes between 4 weeks diabetic rats and age-matched control rats. These results indicate that abnormal gene expressions of BM components and type I collagen might play an important role in the initiation of glomerular changes in diabetes.
 ...
PMID:[Altered glomerular mRNA expression of basement membrane components and type I collagen in diabetic rats treated with or without insulin therapy]. 206 13

We examined steady-state levels of mRNA encoding type IV collagen, B1 chain of laminin, and the basement membrane heparan sulfate proteoglycan in the kidney cortex of a mouse model (KKAy) of non-insulin-dependent diabetes. mRNAs encoding laminin B1 and the proteoglycan were unchanged in kidneys taken from diabetic mice with demonstrable basement membrane thickening. mRNA levels for type IV collagen, in contrast, were significantly elevated (2-fold) in diabetic mice concurrent with but not preceding morphologically thickened basement membranes. There was a negative correlation between a ratio of proteoglycan/type IV collagen and levels of albuminuria in the diabetic mice. No correlation was noted with laminin. We also examined the effects of inhibiting the synthesis of thromboxane, a potent vasoconstrictor, on the steady-state levels of type IV collagen in the diabetic mice. Inhibition of thromboxane stopped the progression of albuminuria and prevented an increase in type IV collagen mRNA levels. We conclude that basement membrane thickening in diabetes, a hallmark of diabetic nephropathy, is partly a consequence of an unbalanced increase in the production of type IV collagen. The relative decrease in proteoglycan production may contribute to chronic albuminuria.
 ...
PMID:Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. 222 27

Administration of advanced glycosylation end products (AGEs), prepared on mouse albumin, to normal young adult mice, resulted in an increase in mean glomerular volume and up-regulation of laminin B1 and alpha 1 type IV collagen mRNAs measured by competitive PCR in single microdissected glomeruli. Both glomerular hypertrophy and overexpression of genes coding for extracellular matrix were abrogated when aminoguanidine, an inhibitor of AGE cross-linking, was added to the AGEs injections, suggesting that the glomerular response to AGEs was specific. The effects of AGEs administration in vivo are comparable to those occurring in the early stage of diabetic nephropathy, suggesting a participation of AGEs in these events.
 ...
PMID:Administration of AGEs in vivo induces genes implicated in diabetic glomerulosclerosis. 767 96