Abstract:
Purpose:To investigate the molecular pathways that drive thyroid stimulating hormone receptor (TSHR)-induced cellular proliferation in orbital fibroblasts (OFs) from thyroid eye disease (TED) patients. Methods:Orbital fibroblasts from TED and non-TED patients were treated with TSH and changes in gene expression and proliferation were measured. To determine the role of TSHR, TSHR-specific siRNA was used to deplete TSHR levels. Proliferation was measured by bromodeoxyuridine (BrdU) incorporation. PI3K/Akt activation was analyzed by Western blot. The PI3K inhibitor LY294002 was used to investigate PI3K/Akt signaling in OF proliferation. Expression of TSHR, inflammatory cytokines, proliferation related genes and miR-146a and miR-155 were measured by qPCR. Results:Orbital fibroblasts from TED patients proliferate significantly more than non-TED OFs in response to TSH. TSH-induced proliferation was dependent upon TSHR expression and required the PI3K/Akt signaling cascade. TSHR activation stimulated miR-146a and miR-155 expression. TED OFs produced significantly more miR-146a and miR-155 than non-TED OFs. MiR-146a and miR-155 targets, ZNRF3 and PTEN, which both limit cell proliferation, were decreased in TSH treated OFs. Conclusions:These data reveal that TSHR signaling in TED OFs stimulates proliferation directly through PI3K/Akt signaling and indirectly through induction of miR-146a and miR-155. MiR-146a and miR-155 enhance TED OF proliferation by reducing expression of target genes that normally block cell proliferation. TSHR-dependent expression of miR-146a and miR-155 may explain part of the fibroproliferative pathology observed in TED.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Woeller CF,Roztocil E,Hammond C,Feldon SEdoi
10.1167/iovs.19-27865subject
Has Abstractpub_date
2019-10-01 00:00:00pages
4336-4345issue
13eissn
0146-0404issn
1552-5783pii
2753387journal_volume
60pub_type
杂志文章abstract::Topical administration of biosynthetic human epidermal growth factor (h-EGF), given in combination with an antibiotic and synthetic steroid (Neodecadron) accelerated the rate of corneal epithelial regeneration and significantly increased the strength of full-thickness stromal incisions in primates. The regenerated epi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Glaucoma is a distinct neuropathy characterized by the chronic and progressive death of retinal ganglion cells (RGCs). The etiology of RGC death remains unknown. Risk factors for glaucomatous RGC death are elevated intraocular pressure and glial production of tumor necrosis factor-alpha (TNF-α). Previously, the...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5431
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract:PURPOSE:The purpose of this study was to determine whether clinical signs of infectious keratitis can be used to identify the causative organism. METHODS:Eighty photographs of eyes with culture-proven bacterial keratitis or smear-proven fungal keratitis were randomly selected from 2 clinical trials. Fifteen cornea spe...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1167/iovs.11-8478
更新日期:2012-04-02 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0254
更新日期:2005-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract:PURPOSE:The organization of scleral collagen helps to determine the eye's biomechanical response to intraocular pressure (IOP), and may therefore be important in glaucoma. This study provides a quantitative assessment of changes in scleral collagen fibril organization in bead-induced murine experimental glaucoma. METH...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15047
更新日期:2014-09-16 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract:PURPOSE:It has been suggested that early menopause increases the risk of aging-macula disorder (AMD), the major cause of incurable blindness with a dry and wet late subtype, and that exposure to endogenous or postmenopausal exogenous estrogens reduces this risk. This study was undertaken to investigate whether genetic ...
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doi:10.1167/iovs.06-0577
更新日期:2007-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract:PURPOSE:This study was designed to investigate the suppressive effects of antithrombin (AT)III on inflammatory reactions during endotoxin-induced uveitis (EIU) in rats by studying leukocyte-endothelium interactions. METHODS:EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). ATIII was admin...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1167/iovs.14-14940
更新日期:2014-08-07 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract:Purpose:To radiologically examine for the presence of bony remodeling of the orbit in thyroid eye disease (TED). Methods:Computed tomography (CT) scans of 248 orbits of 124 patients with TED and 185 orbits of 138 controls were retrospectively reviewed, and the following parameters measured: the angle of the inferomedi...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1979-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2011-02-09 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2017-03-01 00:00:00
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更新日期:2002-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2003-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00