Differential Effect of Growth Factors on Hyaluronan Synthase Gene Expression in Fibroblasts Exposed to Oxidative Stress

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G. M. Campo^1*, A. Avenoso¹, S. Campo¹, A. D'Ascola¹, A. M. Ferlazzo², and A. Calatroni¹

¹Department of Biochemical, Physiological, and Nutritional Sciences, School of Medicine, University of Messina, Policlinico Universitario, Torre Biologica, 5° piano, Via C. Valeria, 98125 Messina, Italy; fax: +39-90-221-3330; E-mail: gcampo@unime.it

²Department of Morphology, Biochemistry, Physiology and Animal Production, School of Veterinary Medicine, University of Messina, Contrada Annunziata, 98168 Messina, Italy

^* To whom correspondence should be addressed.

Received April 26, 2007

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The aim of this study was to evaluate how growth factors (PDGF-BB, EGF, and TGF-1beta) modulate hyaluronan synthase (HAS) activities in normal or stressed cultured human skin fibroblasts. The effects of concomitant treatment with cytokines and FeSO₄ plus ascorbate on HAS mRNA expression, protein synthesis, and hyaluronic acid (HA) concentrations were also studied. Treatment of fibroblasts with growth factors up-regulated HAS gene expression and increased HAS enzymes and HA production. PDGF-BB induced HAS mRNA expression, protein synthesis, and HA production more efficiently than EGF and TGF-1beta. EGF was less effective than TGF-1beta. In addition, TGF-1beta reduced the expression and synthesis of HAS3, while PDGF-BB and EGF had the opposite effect. Concomitant treatment with growth factors and the oxidant was able to further increase HAS mRNA expression, once again with the exception of HAS3 with TGF-1beta. HAS protein synthesis was reduced, while HA levels were unaffected in comparison to those obtained from exposure to FeSO₄ plus 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 increase in HAS mRNA levels was not translated into a consequent rise in HA concentration.

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KEY WORDS: free radicals, glycosaminoglycans, growth factors, cell cultures, fibroblasts, hyaluronan synthases, hyaluronan, PDGF-BB, EGF, TGF-1beta

DOI: 10.1134/S0006297907090088

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