Effects and Its Mechanism of IGF-1R on the Synthesis of Hyaluronic Acid in Orbital Fibroblasts of

【Abstract】 Objective To explore the effects of insulin-like growth factor1 (IGF1) receptor (IGF1R) on the synthesis of hyaluronic acid (HA) in orbital fibroblasts of thyroid associated ophthalmopathy （TAO） and its signal pathway. Methods Orbital fibroblasts were harvested from TAO ( n=19) and normal control ( n=5), then were primary cultured and treated with recombinant human IGF1 in different concentrations. Before the treatment of IGF1, the cells were pretreated respectively with 1H7, LY294002 or AKT inhibitor Ⅳ for 24 h. The production of HA was measured using a commercial ELISA kit, and the synthesis of PI3K, Akt and pAkt was measured by Western blot. Results Along with the increase of recombinant human IGF1 concentration, the synthesis of HA by TAO orbital fibroblasts were increased as well,the synthesis of HA peaked at the concentration of 10 nmol/L in IGF1 in TAO group （ P＜0.01). Compared with the normal control, orbital fibroblasts from TAO had the synthesis of HA increased after the treatment of IGF1 ( P＜0.01). The pretreatment of 1H7 or AKT inhibitor Ⅳ significantly decreased the HA concentration in culture media ( P＜0.01), while the decrease of HA synthesis in the group pretreated with LY294002 was not statistically significant ( P=0.390). IGF1 treatment increased the level of pAkt expression, but it seems no effects on PI3K and Akt expression. 1H7 and LY294002 decreased the expression of PI3K and pAkt protein, but no obvious inhibitory effect on total Akt protein. Akt inhibitor Ⅳ decreased the expression of PI3K, Akt and pAkt. Conclusion The synthesis of HA by orbital fibroblasts could be increased in TAO, which may partially via phosphoinositide 3kinase/Akt pathway.