Differential effect of growth factors on hyaluronan synthase gene expression in fibroblasts exposed to oxidative stress

The aim ofthis study was to evaluate how growth factors (PDGF-BB, EGF, and TGF-1) modulate hyaluronan synthase (HAS) activities in norma1 or stressed cu1tured human skh1 fibroblasts. The etfects of concomitant treatment with cytokines and FeS04 plus ascorbate on HAS mRNA expression, protem synthesis, and hya1uronic acid (HA) concentrations were also studied. Treatment of fibroblasts with growth factors up-regu1ated HAS gene expression and increased HAS enzymes and HA production. PDGF-BB induced HAS mRNA expression, protein synthesis, and HA production more effi­ ciently than EGF and TGF-1. EGFwas Jess eflective than TGF-1. In addition, TGF-1reduced the expression and syn­ thesis ofHAS3, while PDGF-BB and EGF had the apposite effect. Concomitant treatment with growth factors and the oxi­ dant was able to further increase HAS mRNA expression, once again with the exception ofHAS3 with TGF-1. HAS pro­ tem synthesis was reduced, while HA Jevels were unaffected in comparison to those obtained from exposure to FeS0 4 p1us ascorbate alone. In conclusion, although growth factors plus the oxidant synergistically induced HAS mRNA expression in part, enzyme production was not correlated with this increase. Moreover, the h1crease m HAS mRNA Jevels was not trans­ lated into a consequent rise in HA concentration.