Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts

Abstract

Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.

Thy-1 Expression in Human Fibroblast Subsets Defines Myofibroblastic or Lipofibroblastic Phenotypes

“…41,42 Little is known about reproductive tract fibroblasts, but orbital fibroblasts are also different from fibroblasts derived from other tissues. 7,30,36,43 Since each organ exhibits unique functions to maintain normal physiology, it is expected that fibroblasts derived from different tissues will be functionally diverse. Our observations in the present study support the concept of "tissue-specific" fibroblasts, since human Thy-1 ϩ myometrial fibroblasts express ␣SMA in a constitutive, heterogeneous manner, a feature missing from human orbital Thy-1 ϩ fibroblasts.…”

“…35,36 Briefly, myometrial tissue biopsies were collected from women undergoing gynecological procedures for benign conditions. All women had regular menstrual cycles (25 to 35 days), were pre-menopausal (20 to 42-years-old), and did not receive any form of hormonal treatment 3 months before the procedure.…”

Significance of Thyroid Stimulating Antibody and Long Term Follow Up in Patients with Euthyroid Graves' Disease.

“…Though the pathogenesis of Graves' ophthalmopathy is still unclear, many investigators have proposed an autoimmune mechanism [29][30][31][32][33][34][35][36][37][38][39][40]. As the histological evidence of autoimmunity, lymphocyte and macrophage infiltration and peptide factors such as IL-1a, TNFa, IFNy, TGF/3, PDGF and IGF-I, were detected in retroorbital tissues [41][42][43][44].…”

Synovial Fibroblasts from Patients with Rheumatoid Arthritis, Like Fibroblasts from Graves’ Disease, Express High Levels of IL-16 When Treated with Igs against Insulin-Like Growth Factor-1 Receptor

“…These cells exhibit several phenotypic attributes similar to those from other regions of the body, including the expression of cytokine-dependent IL-16 and RANTES (8). Orbital fibroblasts from patients with GD were obtained from individuals undergoing decompressive surgery for severe thyroid-associated ophthalmopathy, as described previously (20). They have been characterized extensively (21).…”