High glucose increases growth and collagen synthesis in cultured human tubulointerstitial cells

Aims Altered proximal tubular cell growth and interstitial fibrosis are fea tures of diabetic nephropathy and correlate with disease progression. These observations are poorly understood, although it has been suggested that th ey are secondary to glomerular disease. The primary aim of this study was t o assess the direct effects of high extracellular glucose concentrations on the human tubulointerstitium. Methods Primary cultures of human proximal tubule cells (PTCs) and cortical fibroblasts (CFs) were grown for 6 days in media containing either 6.1 mol /l or 25mmol/l glucose. Cell proliferation, thymidine uptake (a marker-of D NA synthesis), protein content and collagen synthesis were measured. Results In PTCs, exposure to high glucose was associated with a 410 +/- 108 % increase in cell numbers (P < 0.001); 101 +/- 24% increase in thymidine u ptake per cell (P < 0.01) and a 39 +/ -6% decease in protein content per ce ll (P < 0.05). Collagen synthesis was increased by 37 +/- 11% (P <0.05). In CFs, exposure to high glucose was associated with an 80 +/- 25% increase i n cell numbers (P <0.05); 137+50% increase in thymidine uptake per cell (P < 0.001), with protein content per cell unchanged. Collagen synthesis incre ased by 37 +/- 13%; however, the difference was not significant (P = 0.07). There were no differences between control cells exposed to 6.1 mmol/l gluc ose or an osmotic control (6.1 mmol/l D-glucose + 18.9 mmol/l L-glucose). Conclusions Exposure of human PTCs and CFs to high extracellular glucose co ncentrations results directly in altered cell growth and collagen synthesis that is independent of haemodynamic, glomerular or vascular pathology.