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

Summary Aims Altered proximal tubular cell growth and interstitial fibrosis are features of diabetic nephropathy and correlate with disease progression. These observations are poorly understood, although it has been suggested that they are secondary to glomerular disease. The primary aim of this study was to 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 mmol/l or 25 mmol/l glucose. Cell proliferation, thymidine uptake (a marker of DNA 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 uptake per cell (P < 0.01) and a 39 ± 6% decease in protein content per cell (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 in cell numbers (P < 0.05); 137 ± 50% increase in thymidine uptake per cell (P < 0.001), with protein content