| Purpose: To investigate the effects of insulin-like growth factor (IGF)-1 and somatostatin on the proliferation and the expression of hyaluronan synthase(HAS) mRNA of the orbital fibroblasts from the patients of thyroid-associated ophthalmopathy(TAO).Methods: Orbital fibroblasts obtained from 4 patients with TAO were cultured. The effects of IGF—1 and somatostatin on the proliferation of the fibroblasts were compared with MTT colorimetry assays. The expression of HAS mRNA in the orbital tissues from patients and normal controls was examined by real-time PCR. The effects of IGF—1 and somatostatin on the expression of HAS mRNA in the fibroblast was also examined by RT-PCR. Results: (1) The orbital fibroblasts were successfullycultured. (2) IGF-1 induced the proliferation of the orbital fibroblasts, while Somatostatin suppressed the proliferation of the orbital fibroblasts. Somatostatin in high concentration blocked the induction of IGF-1 on the proliferation of the fibroblasts. (3) HAS3 mRNA was detected by RT-PCR in all tissue blocks from TAO patients and normal subjects. HAS1 mRNA was detected in 9 blocks from the 14 patients, and 4 from the 8 controls.HAS2 mRNA was detected in 2 blocks from the patients , and 3 from the controls. But the differences in the positive rates was not significant. The quantity of HAS1 and HAS3 mRNA copies in patients was 8 and 4. 5 times of normal controls, respectively. (4)IGF-1 had no effect on the expression of HAS1 mRNA in all 4 cell strains. IGF-1 down-regulated the expression of HAS2 mRNA, but up-regulated the expression of HAS3 mRNA. (5)Somatostatin had no effect on the expression of HAS1.HAS2, and HAS3 mRNA, but in high concentration, it blocked the effects of IGF-1 on the expression of HAS genes completely.Conclusions: Our observations suggest that IGF-1 may play a role in the pathogenesis of TAO. The suppressive effects of somatostatin on the role of IGF-1 may be the molecular basis for its therapeutic effects on TAO. |
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