Changes in Expression of the Connective Tissue Growth Factor in the Kidneys of Diabetic Rats During Aging

Abstract

Background: Diabetic nephropathy (DN) is the most common cause of chronic renal failure in the world. There appears to be different pathogenetic, hemodynamic and metabolic processes leading to the pathologic mechanisms in DN. We studied the expression of connective tissue growth factor (CTGF) in the kidneys of diabetic rats over time.Methods: Male Sprague-Dawley rats were injected with 55mg/kg streptozotocin (STZ) (diabetes mellitus (DM) group) or with citrate buffer (control group). The rat kidneys were harvested 2 weeks, 2 months, 6 months and 12 months following the STZ challenge, and sectioned into three different kidney structures: glomeruli, proximal convoluted tubule (PCT) and distal convoluted tubule (DCT). Sections were immunohistochemically stained to monitor the expression of CTGF. Results:Significant differences in CTGF expression were observed 2 weeks and 2 months after the STZ challenge, with higher CTGF expression in diabetic rats. Two weeks post DM onset, high CTGF expression was demonstrated in the distal tubules of the diabetic rats. The expression of CTGF in the glomeruli of diabetic rats washighest 12 months after diabetes induction, with a complete absence of CTGF expression in the control groups throughout the study.Conclusions:The major change in expression of CTGF occurs within the first 2 months of DM, particularly in the DTC, implying an early onset of pathophysiological changes in diabetic kidneys, which would normally occur with aging. These findings help to contribute to our understanding of changes associated with DN and guide towards potentially appropriate treatment modalities.Key words: diabetes mellitus (DM), nephropathy, chronic renal failure, connective tissue growth factor (CTGF)