Effects of Dibutyryl Cyclic AMP on Hyaluronan and Proteoglycan Synthesis by Retroocular Tissue Fibroblasts in Culture

Endocrine Journal

YUMI IMAI²  RITSUKO ODAJIMA¹  YOSHIMASA SHISHIBA¹  KYOMI IBARAKI² 

[1] Division of Endocrinology, Department of Medicine, Toranomon Hospital;Bone Research Branch, National Institute of Dental Research, National Institutes of Health

关键词: cAMP;    Hyaluronan;    Proteoglycan;    Glycosaminoglycan;    Retroocular fibroblast;    Graves' disease;   

DOI  :  10.1507/endocrj.41.645

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(24)Cited-By(6)Deposition of glycosaminoglycan is one of the histological features of Graves' ophthalmopathy. Although retroocular tissue fibroblasts are considered to be responsible for glycosaminoglycan accumulation, it is not known what is stimulating the fibroblasts. There are studies which are in support of and against the role of and-TSH receptor antibodies in the pathogenesis of Graves' ophthalmopathy. TSH-receptor antibodies increase cAMP as a second messenger in thyroid cells. We studied the effects of dibutyryl cyclic AMP (Bt2 cAMP) on glycosaminoglycan synthesis by retroocular tissue fibroblasts in order to know whether cAMP can modulate glycosaminoglycan synthesis. Retroocular tissue fibroblasts mainly synthesize hyaluronan, the large chondroitin sulfate proteoglycan and the small chondroitin sulfate proteoglycan as glycosaminoglycan in cell culture. The amount of hyaluronan synthesis was measured as [3H] glucosamine incorporation into macromolecule susceptible to hyaluronidase digestion (from Streptomyces hyaluronlyticus). The amount of proteoglycan synthesis was measured as [35S] sulfate incorporation into macromolecules in medium and cell layer fraction. Proteoglycans in medium were further separated into the large proteoglycan and the small proteoglycan on a Superose 6 column. Bt2 cAMP increased both hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts, especially stimulating the secretion of the large proteoglycan. Effects of Bt2 cAMP on glycosaminoglycan synthesis were then compared with those in adult skin fibroblasts. Although the magnitude of response between the two was indistinct, the stimulation of the large proteoglycan synthesis by Bt2 cAMP was more prominent in retroocular tissue fibroblasts. The results suggest that the regulation of glycosaminoglycan synthesis by retroocular tissue fibroblasts is different from that by adult skin fibroblasts. Although further studies are required to determine its actual role, cAMP stimulates glycosaminoglycan synthesis by retroocular tissue fibroblasts and underlies the mechanism in Graves' ophthalmopathy.

【 授权许可】

Unknown