Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts - PubMed (original) (raw)
Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts
T J Smith et al. J Clin Endocrinol Metab. 1995 Sep.
Abstract
Orbital fibroblasts in culture display phenotypic attributes that distinguish them from fibroblasts derived from other anatomical regions. The current studies were conducted to define potential cellular heterogeneity among orbital fibroblasts with regard to 1) differential expression of Thy-1, a 25-kilodalton glycoprotein associated with cell signaling; 2) cells undergoing a change in shape in response to prostaglandin E2 (PGE2); and 3) differences in morphology and Thy-1 expression between single cell-derived clonal fibroblast strains. On the basis of flow cytometric analysis using an anti-Thy-1 monoclonal antibody, 65% of intact orbital fibroblasts expressed surface Thy-1 (n = 5; range, 54-71%). In contrast, greater than 95% of the fibroblasts present in the five dermal strains tested were Thy-1 positive. A total of six strains of orbital fibroblasts were assessed for their shape change response to a 4-h treatment with PGE2 (100 nmol/L). A mean of 37% of the fibroblasts present in each culture responded to PGE2 (range, 22-50%). In contrast, only 1% of dermal fibroblasts exhibited any change in morphology. Three separate clones were generated from a single parent strain of Graves' orbital fibroblasts. These clones consisted of homogeneous appearing cells; however, substantial clone to clone differences in morphology were stably expressed for several population doublings. Thy-1 was expressed uniformly in cells of two clones, whereas the third was Thy-1 negative. Factor VIII and smooth muscle-specific alpha-actin were undetectable in any of the orbital or dermal cultures examined. Thus, Thy-1 expression is uniform in fibroblasts from certain anatomical regions such as the skin and heterogeneous in cells derived from human lung and orbit. These findings suggest that human orbital connective tissue may have a complexity not previously appreciated.
Similar articles
- Prostaglandin E2 alters human orbital fibroblast shape through a mechanism involving the generation of cyclic adenosine monophosphate.
Wang HS, Keese CR, Giaever I, Smith TJ. Wang HS, et al. J Clin Endocrinol Metab. 1995 Dec;80(12):3553-60. doi: 10.1210/jcem.80.12.8530598. J Clin Endocrinol Metab. 1995. PMID: 8530598 - Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy.
Smith TJ, Koumas L, Gagnon A, Bell A, Sempowski GD, Phipps RP, Sorisky A. Smith TJ, et al. J Clin Endocrinol Metab. 2002 Jan;87(1):385-92. doi: 10.1210/jcem.87.1.8164. J Clin Endocrinol Metab. 2002. PMID: 11788681 - Assessment of rapid morphological changes associated with elevated cAMP levels in human orbital fibroblasts.
Reddy L, Wang HS, Keese CR, Giaever I, Smith TJ. Reddy L, et al. Exp Cell Res. 1998 Dec 15;245(2):360-7. doi: 10.1006/excr.1998.4273. Exp Cell Res. 1998. PMID: 9851877 - Unique properties of orbital connective tissue underlie its involvement in Graves' disease.
Smith TJ. Smith TJ. Minerva Endocrinol. 2003 Sep;28(3):213-22. Minerva Endocrinol. 2003. PMID: 14605603 Review. - The putative role of prostaglandin endoperoxide H synthase-2 in the pathogenesis of thyroid-associated orbitopathy.
Smith TJ. Smith TJ. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 5:S160-3. doi: 10.1055/s-0029-1212175. Exp Clin Endocrinol Diabetes. 1999. PMID: 10614912 Review.
Cited by
- Fibrocyte Participation in Thyroid-Associated Ophthalmopathy Suggests New Approaches to Therapy.
Smith TJ. Smith TJ. Ophthalmic Plast Reconstr Surg. 2023 Dec 1;39(6S):S9-S18. doi: 10.1097/IOP.0000000000002509. Epub 2023 Dec 4. Ophthalmic Plast Reconstr Surg. 2023. PMID: 38054981 Review. - The Role of Interleukin-17A and NLRP3 Inflammasome in the Pathogenesis of Graves' Ophthalmopathy.
Lin CC, Liao SL, Wei YH. Lin CC, et al. Life (Basel). 2023 Apr 13;13(4):1007. doi: 10.3390/life13041007. Life (Basel). 2023. PMID: 37109536 Free PMC article. - Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease.
Smith TJ. Smith TJ. J Clin Endocrinol Metab. 2022 Aug 8;107(Suppl_1):S13-S26. doi: 10.1210/clinem/dgac328. J Clin Endocrinol Metab. 2022. PMID: 36346686 Free PMC article. - Teprotumumab Divergently Alters Fibrocyte Gene Expression: Implications for Thyroid-associated Ophthalmopathy.
Fernando R, Smith TJ. Fernando R, et al. J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4037-e4047. doi: 10.1210/clinem/dgac415. J Clin Endocrinol Metab. 2022. PMID: 35809263 Free PMC article. - Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves' Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways.
Wei YH, Liao SL, Wang SH, Wang CC, Yang CH. Wei YH, et al. Front Endocrinol (Lausanne). 2021 Feb 1;11:607968. doi: 10.3389/fendo.2020.607968. eCollection 2020. Front Endocrinol (Lausanne). 2021. PMID: 33597925 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous