Hyperglycaemia and tubulointerstitial fibrosis in renal proximal tubular epithelial cells.
F Alsehli, N Ahmed and L Shalamanova
Centre for Biomedicine, School of Healthcare Science, Manchester Metropolitan University, Manchester, UK
Background: Renal tubulointerstitial fibrosis (TIF) is the hallmark of chronic and end-stage renal disease. Around 40% of the diabetic patients develop diabetic nephropathy which is characterised by abnormal accumulation of extracellular matrix in the nephron. The aim of this study is to determine the mechanisms of hyperglycaemia induced TIF in renal proximal tubular epithelial cells.
Methods: HK-2 cells were exposed to different concentrations of glucose (5, 25, 30mM D-glucose and 5mM D-glucose+25mM L-glucose). Glucose consumption, scratch wound healing, cell proliferation, PAI-1, TGF-β1, endostatin and KIM-1/TIM-1 expression were measured at up to 72h of hyperglycaemia.
Results: Reduced glucose consumption and wound healing were observed at 30mM D-glucose. In contrast, the wound healing was accelerated at 25mM D-Glucose. Although TGF-β1 levels were significantly increased by 30mM D-glucose and the osmotic control 5mM D-glucose+25mM L-glucose, TGF-β1 was reduced by 25mM D-glucose. Furthermore, hyperglycaemia had no effect on the markers of renal injury endostatin and KIM-1/TIM-1.
Conclusion: Hyperglycaemia does not induce the expression of markers of kidney injury. However, the data demonstrate a critical threshold (between 25mM and 30mM glucose), which triggers the release of TGF-β1 and potentially promotes TIF in HK-2 cells. Further studies are required to elucidate the detailed mechanisms of this process.