Anti-NOS3 monoclonal antibody, clone 7I3

Type-2 diabetes (T2D) is a multifactorial (environmental and genetic factors) and global epidemic disease with an estimated high prevalence worldwide. Studies have indicated that nitric oxide synthase 3 (NOS3) has several important roles in the pathogenesis of T2D. The present study aims to investigate the association between NOS3 rs1800779(A/G) and T2D in an Iranian sample population. A case-control study was conducted on 250 T2D patients and 250 healthy control subjects (HCs). Genotyping of the rs1800779(A/G) variant was conducted using a Tetra-Amplification Refractory Mutation System polymerase chain reaction. The frequencies of genotypes AA, AG and GG polymorphisms were 56.8, 39.2 and 4% in the T2D group, and 42.8, 56 and 1.2% in the HCs group, respectively. The frequency of the minor (G) allele was 23.6% in the T2D group and 29.2% in the HCs group. The genotype frequencies of the rs1800779(A/G) variant demonstrated statistically significant differences between T2D and controls in a codominant model (AG vs. AA, OR=0.527, 95% CI=0.368-0.756, P<0.001) and dominant model (AG+GG vs. AA, OR=0.569, 95% CI=0.399-0.811, P=0.002). There was no significant association between clinical and demographic characteristics and the NOS3 rs1800779(A/G) polymorphism in dominant status (P>0.05). The dominant model and AG genotype of NOS3 rs1800779(A/G) polymorphism may had a protective effect on T2D of Iranian population.

Loss of functional nephrons induces compensatory glomerular hyperfiltration and hypertrophy, leading to the progression of chronic kidney disease. Kruppel-like factor 2 (KLF2), a shear-stress inducible transcription factor, confers protection against endothelial injury. Because glomerular hyperfiltration is associated with shear stress, we hypothesized that KLF2 may be an important factor in the compensatory response to unilateral nephrectomy (UNX). To test this hypothesis, endothelial cell specific Klf2 heterozygous knockout mice (KO) and their wild-type Littermate control (WT) underwent either UNX or sham-operation. WT-UNX mice developed compensatory renal hypertrophy as expected, whereas K0-UNX mice did not. K0-UNX mice exhibited higher blood pressure, reduced glomerular filtration rate, and significant increase in proteinuria and glomerulosclerosis compared to WT-UNX. Expression of endothelial nitric oxide synthase (official name Nos3), a known transcriptional target gene of KLF2, was significantly reduced and dysregulation of other endothelial genes was also observed in the glomeruli of K0-UNX when compared to WT-UNX and sham-operated mice. Furthermore, both podocyte number and expression of podocyte markers were also significantly reduced in K0-UNX glomeruli, indicating a potential cross talk between glomerular endothelial cells and podocytes. Finally, decreased renal expression of KLF2 in nephrectomy patients was associated with the progression of kidney disease. Taken together, our data demonstrate a protective role of KLF2 against glomerular endothelial cell injury and progression of chronic kidney disease in the model of compensatory renal hypertrophy.