Sdf-1 And Diabetic Nephropathy

Aims Stromal cell-derived factor 1 (SDF-1) is a chemokine with multiple roles in cell homing, tumor metastasis, angiogenesis and tissue regeneration in acute injuries, whereas the role of SDF-1 in diabetic nephropathy has not been illustrated distinctly. We hypothesized that SDF-la may have an effect on mesangial extracellular matrix (ECM) accumulations in mesangial cells exposed to TGF-β1 or high glucose in vitro and studied the mechanisms.Methods Rat mesangial cells (HBZY-1) were cultured in vitro and we tested the mRNA expressions of fibronectin (FN), CXCR4, SDF-1αin mesangial cells by RT-PCR; After incubated in high concentration of glucose or TGF-(31 and SDF-la for indicated times, we determined the expressions of CXCR4, FNmRNA in mesangial cells by real-time PCR and western blotting; We interferred the mesangial cells with PI3K inhibitor LY294002 or CXCR4 blocker AMD3100 at the same time, and determined the expressions of CXCR4, FNmRNA in mesangial cells by real-time PCR and FN, pSmad3, pAkt by western blotting.Results SDF-la, CXCR4, and FN mRNA were expressed in rat mesangial cells. Both TGF-β1 and high glucose raised the mRNA expressions of CXCR4 and FN in rat mesangial cells. After exposed to TGF-β1 and high concentration of glucose for 72h, the expression of FN was increased in mesangial cells, which can be reduced by SDF-1αwhen cells were incubated with SDF-la at the same time. SDF-la can activate the PI3K/Akt pathway, upregulate the pAkt expression, In mesangial cells exposed to TGF-β1 or high concentration of glucose and SDF-1α, the reduction of SDF-1αon elevated FN was blocked by LY294002. Meanwhile the CXCR4 blocker AMD3100 only partly inhibited the role of SDF-1α. In cells exposed to high concentration of glucose, CXCR4 blocker AMD3100 and LY294002 blocked the reduction of SDF-1αon the extracellular matrix accumulations. In mesangial cells incubated with SDF-1αalone, the expression of FNmRNA had no change. In mesangial cells incubated with LY294002 or AMD3100 alone, the expression of FNmRNA was elevated.Conclusions SDF-laameliorates TGF-β1/high glucose induced ECM accumulations in mesangial cells, which may mediated through PI3K/Akt pathway. This novel mechanism may bring a new insight into our understandings of diabetic nephropathy.