Our results demonstrate that HG-induced cholesterol accumulation and cellular injury in podocytes may be related to the recycling disorder of ABCA1 caused by the downexpression of Arf6 in DKD.
Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD.
We demonstrated that this pathway is relevant to DKD and that ABCA1 inducers or inhibitors of cardiolipin peroxidation may each represent therapeutic strategies for the treatment of established DKD.
Fourth, clinical and experimental evidence support a role for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney disease.
In this study we investigated the effect of exendin-4 on ABCA1 in glomerular endothelial cells of diabetic kidney disease (DKD) and the possible mechanism.
Among all subjects, by univariate linear regression analysis, glomerular MRP8-positive cell count and tubulointerstitial MRP8-positive area at baseline were both, respectively, correlated not only with various known risk factors for diabetic nephropathy (such as systolic blood pressure, proteinuria and serum creatinine) but also with extent of glomerulosclerosis and tubulointerstitial fibrosis.
Among all subjects, by univariate linear regression analysis, glomerular MRP8-positive cell count and tubulointerstitial MRP8-positive area at baseline were both, respectively, correlated not only with various known risk factors for diabetic nephropathy (such as systolic blood pressure, proteinuria and serum creatinine) but also with extent of glomerulosclerosis and tubulointerstitial fibrosis.
Lipid accumulation is ahead of epithelial-to-mesenchymal transition and therapeutic intervention by acetyl-CoA carboxylase 2 silence in diabetic nephropathy.
We have identified the acetyl-coenzyme A carboxylase beta gene (ACACB) as a strong susceptibility gene to diabetic nephropathy in individuals with type 2 diabetes.
To date, case-control studies on the association between a single-nucleotide polymorphism (SNP), rs2268388, in the acetyl-coenzyme A carboxylase beta (ACACB) gene and diabetic nephropathy have provided controversial results.
To investigate the biological roles of ACCβ in the pathogenesis of diabetic nephropathy, we examined the effects of overexpression of ACACB using podocyte-specific ACACB-transgenic mice or ACACB-overexpressing murine podocytes.
Res also decreased DN induced mTOR/ULK1-mediated autophagy and apoptosis and significantly reduced STZ mediated lipid deposition in nephrons, likely by decreasing the levels of lipogenic related proteins (SREBP-1c, ACS) and increased lipidolysis related proteins (PPARα, CPT-1).
The combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy.
The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression.
Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review.
Further, the concomitant study of both systemic and local RAAS, counter-regulators of ACE and ACE2, and also AT1R and angiotensin II type 2 receptor (AT2R) genes could help to elucidate the role of the genes of this system in the pathogenesis of DN.
The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05).