The Effects of Anti-Inflammatory and Anti-Angiogenic DNA Vaccination on Diabetic Nephropathy in Rats

Abstract

Inflammation and angiogenesis play a crucial role in the pathomechanism of diabetic nephropathy. Monocyte chemoattractant protein 1 (MCP) is a key regulator of the immune system in kidneys, and its inhibition with a dominant-negative mutant lacking the N-terminal amino acids 2-8 (7ND) reduces renal fibrosis. Angiomotin (Amot) is a novel angiogenesis modulator. We studied the effects of inhibition of Amot and MCP using DNA vaccination on incipient diabetic nephropathy in rats. Plasmid DNA (with either 7ND or human Amot) was electroporated twice into hind-limb muscles of rats with streptozotocin-induced diabetes mellitus. Sham-electroporated diabetic rats and healthy animals served as controls. After 4 months, renal histology and biochemical analyses were performed. In sham-electroporated diabetic rats, glomerular histology revealed pathological changes. 7ND and Amot treatments reduced glomerular hypertrophy and periodic acid-Schiff positivity. In both treated groups, the expression of profibrotic (transforming growth factor-β, collagen 1), proinflammatory (interleukin-6, tumor necrosis factor-α), and proangiogenic (vascular endothelial growth factor) genes in the renal cortex was lower than in the diabetic group without treatment. The mentioned renoprotective effects could be mediated via higher total antioxidant capacity and improved glycemic control. Anti-angiogenic and anti-inflammatory DNA vaccination ameliorates the progression of glomerular pathology in an animal model of diabetic nephropathy.

Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways

“…Several studies have reported an increase in potent stimulators of angiogenesis in diabetic nephropathy [ 41 , 42 ]. In addition, the therapeutic efficacies of anti–angiogenic strategies have further demonstrated the involvement of angiogenesis in the progression of diabetic nephropathy [ 13 , 43 ]. In this context, genetics of inflammatory cytokines and angiogenesis is important to analyze the involved genes and their role in susceptibility to diabetic nephropathy.…”

“…Chen and Ziyadeh, [ 12 ] reported attenuation of diabetic albuminaria by blockade of VEGF signaling pathway. Further, a recent study showed anti-angiogenic and anti-inflammatory DNA vaccination ameliorates the progression of glomerular pathology in an animal model of diabetic nephropathy [ 13 ]. As inflammation and angiogenesis play a crucial role in the pathomechanism of diabetic nephropathy, many studies have investigated the association of genetic polymorphism in these pathway genes with the risk of diabetic nephropathy.…”

The effects of anthocyanin-rich wheat diet on the oxidative status and behavior of rats

“…Proteinuria was analyzed by the pyrogallol red method ( 34 ). 10 µL of samples were mixed with 300 µL of pyrogallol red reagent (composed from pyrogallol red, methanol, succinic acid, sodium oxalate, sodium benzoate, disodium molybdate, sodium dodecyl sulfate, and Brij 35).…”

Behavioral Changes During Development of Chronic Kidney Disease in Rats

“…Creatinine in urine was assessed by Jaffe method, adding NaOH and picric acid (ratio 5:1) to the samples and measuring the absorbance at 492 nm (25). The concentration of urinary proteins was measured by the pyrogallol red-molybdate method, reading the absorbance at 592 nm (26).…”