Abstract
We investigated the effect of TGF-β1 latency-associated peptide (LAP) on the glucose-induced increase in extracellular matrix proteins in cultured human mesangial cells (MC). Recombinant LAP suppressed TGF-β1 lactivity in the absence of MC in a dose-and time-dependent manner. LAP treatment prevented the TGF-Β1-induced increase in the fibronectin (FN) production of MC. The exposure of MC to 33mM of glucose resulted in an increase in FN and thrombospondin (TSP) production compared to the levels resulting from exposure to5mM of glucose. The glucose-induced overproduction of FN and TSP was completely suppressed by concomitant treatment with LAP. The addition of LAP to MC cultured with a low-glucose media showed no demonstrable effects on the production of FN and TSP.
These results indicate that the glucose-induced increase in FN and TSP production in MC is prevented by LAP through the suppression of TGF-β1 activity. These findings warrant further in vivo study on the effects of LAP in diabetic nephropathy.
