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)

Antisera to rat smooth muscle actomyosin (AMY) and myosin localize in the rat glomercular mesangium. The width of mesangial staining for AMY is increased in rats diabetic for four months (p less than 0.01) and seven months (p less than 0.0005) compared with age-matched controls. Mesangial AMY staining of unilaterally nephrectomized control animals was moderately increased after seven months, whereas unilaterally nephrectomized diabetic rats had prominently increased AMY mesangial width at four months, when they were compared with intact diabetic animals (p less than 0.05). Thus, a distinctive alteration that is found in human diabetic nephropathy also occurs in experimental (streptozotocin) diabetes in the rat. Further, this alteration appears to be accelerated by the changes in nephron hemodynamics resulting from unilateral nephrectomy. While the function of mesangial AMY is unknown, it may be related to intrarenal regulation of glomerular ultrafiltration, which appears to be altered in diabetic nephropathy in man.
 ...
PMID:The immunohistopathology of glomerular antigens. III. Increased mesangial actomyosin in experimental diabetes in the rat. 65 8

Tubulointerstitial fibrosis in diabetic nephropathy (DN) was investigated using an in vitro tissue model of remodeling, to determine the pathogenic mechanism of fibrosis that leads to renal atrophy, i.e., renal failure. The remodeling model consisted of a renal fibroblast-populated collagen lattice (FPCL). The overexpression of transforming growth factor (TGF)-beta1 in the diabetic kidney gave rise to FPCL contraction. FPCL relaxation was induced by the subsequent addition of cytochalasin D. The FPCL failed to contract when exposed to TGF-beta1 plus Y27632, a Rho kinase inhibitor. TGF-beta1 induced the phosphorylation of myosin light chains, and Y27632 blocked this activity. TGF-beta1-induced FPCL contraction was suppressed by the addition of 2,3-butanedione monoxime, a myosin ATPase inhibitor. As shown in the video, the contraction rate of the projections of the cells in the FPCL was significantly greater in the TGF-beta1 group than in the control group. Collectively, these results indicate that TGF-beta1-induced FPCL contraction is attributable to actin-myosin interactions in the fibroblasts through the activation of Rho kinase, the phosphorylation of myosin light chains, and the subsequent activation of myosin ATPase. We propose that via these mechanisms, tubulointerstitial fibrosis generates tissue contraction that leads to renal atrophy and renal failure in DN.
 ...
PMID:Contraction of tubulointerstitial fibrosis tissue in diabetic nephropathy, as demonstrated in an in vitro fibrosis model. 1789 81

Diabetic complications including diabetic nephropathy, retinopathy, and neuropathy are as major causes of morbidity and mortality in diabetes individuals worldwide and current therapies are still unsatisfactory. One of the reasons for failure to develop effective treatment is the lack of fundamental understanding for underlying mechanisms. Genetic studies are powerful tools to dissect disease mechanism. The heritability (h (2)) was estimated to be 0.3-0.44 for diabetic nephropathy and 0.25-0.50 for diabetic retinopathy respectively. Previous linkage studies for diabetic nephropathy have identified overlapped linkage regions in 1q43-44, 3q21-23, 3q26, 10p12-15, 18q22-23, 19q13, 22q11-12.3 in multiple ethnic groups. Genome-wide association studies (GWAS) of diabetic nephropathy have been conducted in several populations. However, most of the identified risk loci could not be replicated by independent studies with a few exceptions including those in ELMO1, FRMD3, CARS, MYO16/IRS2, and APOL3-MYH9 genes. Functional studies of these genes revealed the involvement of cytoskeleton reorganization (especially non-muscle type myosin), phagocytosis of apoptotic cells, fibroblast migration, insulin signaling, and epithelial clonal expansion in the pathogenesis of diabetic nephropathy. Linkage analyses of diabetic retinopathy overlapped only in 1q36 region and current results from GWAS for diabetic retinopathy are inconsistent. Conclusive results from genetic studies for diabetic neuropathy are lacking. For now, small sample sizes, confounding by population stratification, different phenotype definitions between studies, ethnic-specific associations, the influence of environmental factors, and the possible contribution of rare variants may explain the inconsistencies between studies.
...
PMID:Recent progress in the genetics of diabetic microvascular complications. 2606 20