Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

Abstract

The kidney glomeruli are the sites of plasma filtration and production of primary urine. However, they are also the locus of kidney diseases, which progress to chronic renal failure. Glomeruli are a major target of injury in diabetic nephropathy (DN). The mechanisms by which glomerular filtration are regulated are poorly understood, and proteomic investigations of isolated glomeruli on the progressive development of DN in animal models have not been determined. To understand the molecular mechanism leading to DN, especially the glomerular injury mechanism, the differences in the glomerular proteomes of streptozotocin (STZ)-induced-and non-diabetic rats at six and 24 weeks were analyzed via two-dimensional electrophoresis (2-DE). To identify the progressive stages of DN, body weight, blood glucose, and proteinuria were measured periodically, and pathological changes were evaluated by periodic acid-Schiff staining. Magnetic beads were used to isolate glomeruli from kidneys and the glomerular proteomes of non-diabetic and STZ-induced diabetic rats were analyzed by 2-DE and nano-LC-ESI-MS/MS. Glutathione peroxidase 3, peroxiredoxin 2, and histone H2A were down-regulated, and annexin A3 was up-regulated, in the STZ-induced group compared with the controls. Glutathione peroxidase 3 and annexin A3, which might help elucidate the mechanism of DN, were verified by Western blotting. These proteins could potentially provide insight into the mechanism of glomerular injury in DN.

The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome

“…Lower levels of the antioxidant defence protein GPX3 have been reported in the glomeruli of STZ rats compared to healthy control rats (Kim et al. ), which is in agreement with our findings, where liraglutide significantly increased the level of GPX3 compared to the STZ vehicle group (Figure D). GPX3 is mainly produced in the kidney proximal tubules (Avissar et al.…”

“…General traits in the glomeruli from STZ‐induced diabetic rats include decreased capacity of oxidative stress detoxification, increased cell differentiation and possibly renal matrix expansion compared to healthy rats (Kim et al. ). By combining discovery‐based label‐free shotgun mass spectrometry (MS) and multivariate analysis, our aim was to dig deeper into the overall effect of GLP‐1R agonism on the kidney proteome in STZ‐induced diabetic mice.…”