scholarly journals Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

2011 ◽  
Vol 79 (9) ◽  
pp. 3821-3832 ◽  
Author(s):  
Karren M. Plain ◽  
Kumudika de Silva ◽  
John Earl ◽  
Douglas J. Begg ◽  
Auriol C. Purdie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Avium ◽  
Protein Localization ◽  
Clinical Disease ◽  
Intracellular Pathogen ◽  
Mrna Levels ◽  
Content Type ◽  
Mycobacterial Infections ◽  
Indoleamine 2,3 Dioxygenase ◽  
Gene And Protein Expression

ABSTRACTVirulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases.Mycobacterium aviumsubsp.paratuberculosisis an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased inM. aviumsubsp.paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells ofM. aviumsubsp.paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses toM. aviumsubsp.paratuberculosisand other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.

scholarly journals Heterogeneous Expression of the Virulence-Related Adhesin Epa1 between Individual Cells and Strains of the Pathogen Candida glabrata

2011 ◽  
Vol 11 (2) ◽  
pp. 141-150 ◽  
Author(s):  
Samantha C. Halliwell ◽  
Matthew C. A. Smith ◽  
Philippa Muston ◽  
Sara L. Holland ◽  
Simon V. Avery
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Candida Glabrata ◽  
Mrna Levels ◽  
Content Type ◽  
Gene Expression Noise ◽  
Heterogeneous Expression ◽  
Gene Expression Heterogeneity ◽  
Yeast Genes

ABSTRACTWe investigated the relevance of gene expression heterogeneity to virulence properties of a major fungal pathogen,Candida glabrata. The organism's key virulence-associated factors include glycosylphosphatidylinositol-anchored adhesins, encoded subtelomerically by theEPAgene family. Individual-cell analyses of expression revealed very striking heterogeneity for Epa1, an adhesin that mediates ∼95% of adherence to epithelial cellsin vitro. The heterogeneity in Epa1 was markedly greater than that known for other yeast genes. Sorted cells expressing high or low levels of Epa1 exhibited high and low adherence to epithelial cells, indicating a link between gene expression noise and potential virulence. The phenotypes of sorted subpopulations reverted to mixed phenotypes within a few generations. Variation in single-cell Epa1 protein and mRNA levels was correlated, consistent with transcriptional regulation of heterogeneity. Sir-dependent transcriptional silencing was the primary mechanism driving heterogeneous Epa1 expression inC. glabrataBG2, but not in CBS138 (ATCC 2001). Inefficient silencing in the latter strain was not due to a difference inEPA1sequence or (sub)telomere length and was overcome by ectopicSIR3expression. Moreover, differences between strains in the silencing dependence ofEPA1expression were evident across a range of clinical isolates, with heterogeneity being the greatest in strains whereEPA1was subject to silencing. The study shows how heterogeneity can impact the virulence-related properties ofC. glabratacell populations, with potential implications for microbial pathogenesis more broadly.

scholarly journals Positive Regulation of Leptospira interrogans kdp Expression by KdpE as Demonstrated with a Novel β-Galactosidase Reporter in Leptospira biflexa

2012 ◽  
Vol 78 (16) ◽  
pp. 5699-5707 ◽  
Author(s):  
James Matsunaga ◽  
Mariana L. Coutinho
Keyword(s):  
Gene Expression ◽  
Response Regulator ◽  
Regulation Of Gene Expression ◽  
Leptospira Interrogans ◽  
Mrna Levels ◽  
Genetic Circuits ◽  
Positive Regulation ◽  
Content Type ◽  
Novel Approach ◽  
In The Wild

ABSTRACTLeptospirosis is a potentially deadly zoonotic disease that afflicts humans and animals.Leptospira interrogans, the predominant agent of leptospirosis, encounters diverse conditions as it proceeds through its life cycle, which includes stages inside and outside the host. Unfortunately, the number of genetic tools available for examining the regulation of gene expression inL. interrogansis limited. Consequently, little is known about the genetic circuits that control gene expression inLeptospira. To better understand the regulation of leptospiral gene expression, theL. interrogans kdplocus, encoding homologs of the P-type ATPase KdpABC potassium transporter with their KdpD sensors and KdpE response regulators, was selected for analysis. We showed that akdpEmutation inL. interrogansprevented the increase inkdpABCmRNA levels observed in the wild-typeL. interrogansstrain when external potassium levels were low. To confirm that KdpE was a positive regulator ofkdpABCtranscription, we developed a novel approach for constructing chromosomal genetic fusions to the endogenousbgaL(β-galactosidase) gene of the nonpathogenLeptospira biflexa. We demonstrated positive regulation of akdpA′-bgaLfusion inL. biflexaby theL. interrogansKdpE response regulator. A controllipL32′-bgaLfusion was not regulated by KdpE. These results demonstrate the utility of genetic fusions to thebgaLgene ofL. biflexafor examining leptospiral gene regulation.

scholarly journals A Strongly Fluorescing Anaerobic Reporter and Protein-Tagging System forClostridiumOrganisms Based on the Fluorescence-Activating and Absorption-Shifting Tag Protein (FAST)

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Hannah E. Streett ◽  
Katie M. Kalis ◽  
Eleftherios T. Papoutsakis
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Real Time ◽  
Protein Localization ◽  
Anaerobic Conditions ◽  
Reporter System ◽  
Fluorescent Reporter ◽  
Content Type ◽  
Expression Activity ◽  
Microplate Reader

ABSTRACTVisualizing protein localization and characterizing gene expression activity in liveClostridiumcells is limited for lack of a real-time, highly fluorescent, oxygen-independent reporter system. Enzymatic reporter systems have been used successfully for many years withClostridiumspp.; however, these assays do not allow for real-time analysis of gene expression activity with flow cytometry or for visualizing protein localization through fusion proteins. Commonly used fluorescent reporter proteins require oxygen for chromophore maturation and cannot be used for most strictly anaerobicClostridiumorganisms. Here we show that the fluorescence-activating and absorption-shifting tag protein (FAST), when associated with the fluorogenic ligand 4-hydroxy-3-methylbenzylidene-rhodanine (HMBR; now commercially available) and other commercially available ligands, is highly fluorescent inClostridium acetobutylicumunder anaerobic conditions. Using flow cytometry and a fluorescence microplate reader, we demonstrated FAST as a reporter system by employing the promoters of theC. acetobutylicumthiolase (thl), acetoacetate decarboxylase (adc), and phosphotransbutyrylase (ptb) metabolic genes, as well as a mutant Pthland modified ribosome binding site (RBS) versions of Padcand Pptb. Flow cytometry-based sorting was efficient and fast in sorting FAST-expressing cells, and positively and negatively sorted cells could be effectively recultured. FAST was also used to tag and examine protein localization of the predicted cell division FtsZ partner protein, ZapA, to visualize the divisome localization in liveC. acetobutylicumcells. Our findings suggest that FAST can be used to further investigateClostridiumdivisomes and more broadly the localization and expression levels of other proteins inClostridiumorganisms, thus enabling cell biology studies with these organisms.IMPORTANCEFAST in association with the fluorogenic ligand HMBR is characterized as a successful, highly fluorescent reporter system inC. acetobutylicum. FAST can be used to distinguish between promoters in live cells using flow cytometry or a fluorescence microplate reader and can be used to tag and examine protein localization in live, anaerobically grown cells. Given that FAST is highly fluorescent under anaerobic conditions, it can be used in several applications of this and likely manyClostridiumorganisms and other strict anaerobes, including studies involving cell sorting, sporulation dynamics, and population characterization in pure as well as mixed cultures, such as those in various native or synthetic microbiomes and syntrophic cultures.

scholarly journals TRPV Subfamily (TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) Gene and Protein Expression in Patients with Ulcerative Colitis

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Joel J. Toledo Mauriño ◽  
Gabriela Fonseca-Camarillo ◽  
Janette Furuzawa-Carballeda ◽  
Rafael Barreto-Zuñiga ◽  
Braulio Martínez Benítez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Protein Expression ◽  
Gastrointestinal Diseases ◽  
Control Group ◽  
Mrna Levels ◽  
Colonic Tissue ◽  
Formalin Fixed Paraffin ◽  
Gene And Protein Expression ◽  
Formalin Fixed Paraffin Embedded

Introduction. TRPVs are a group of receptors with a channel activity predominantly permeable to Ca2+. This subfamily is involved in the development of gastrointestinal diseases such as ulcerative colitis (UC). The aim of the study was to characterize the gene and protein expression of the TRPV subfamily in UC patients and controls. Methods. We determined by quantitative PCR the gene expression of TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 in 45 UC patients (29 active UC and 16 remission UC) and 26 noninflamed controls. Protein expression was evaluated in 5 μm thick sections of formalin-fixed, paraffin-embedded tissue from 5 customized severe active UC patients and 5 control surgical specimens. Results. TRPV2 gene expression was increased in the control group compared with active UC and remission patients (P=0.002 and P=0.05, respectively). TRPV3 gene expression was significantly higher in controls than in active UC patients (P=0.002). The gene expression of TRPV4 was significantly higher in colonic tissue from patients with remission UC compared with active UC patients (P=0.05) and controls (P=0.005). TRPV5 had significantly higher mRNA levels in a control group compared with active UC patients (P=0.02). The gene expression of TRPV6 was significantly higher in the colonic tissue from patients with active UC compared with the control group (P=0.05). The protein expression of TRPV2 was upregulated in the mucosa and submucosa from the controls compared with the UC patients (P≤0.003). The protein expression of TRPV3 and TRPV4 was upregulated in all intestinal layers from the controls compared with the UC patients (P<0.001). TRPV5 was upregulated in the submucosa and serosa from the controls vs. UC patients (P<0.001). TRPV6 was upregulated in all intestinal layers from the UC patients vs. controls (P≤0.001). Conclusion. The TRPV subfamily clearly showed a differential expression in the UC patients compared with the controls, suggesting their role in the pathophysiology of UC.

scholarly journals Endothelin downregulates SERCA2 gene and protein expression in adult rat ventricular myocytes: regulation by pertussis toxin-sensitive Gi protein and cAMP

2009 ◽  
Vol 296 (3) ◽  
pp. H728-H734 ◽  
Author(s):  
Randa Hilal-Dandan ◽  
Huaping He ◽  
Jody L. Martin ◽  
Laurence L. Brunton ◽  
Wolfgang H. Dillmann
Keyword(s):  
Gene Expression ◽  
Pertussis Toxin ◽  
Ventricular Myocytes ◽  
Intracellular Camp ◽  
Mrna Levels ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Protein Levels ◽  
Gene And Protein Expression ◽  
Gi Protein

Downregulation of the sarcoplasmic reticulum calcium ATPase (SERCA2) is associated with diastolic dysfunction in the failing heart. Elevated plasma endothelin-1 (ET) levels are correlated with congestive heart failure suggesting that ET may play a pathophysiological role. We have investigated the ability of ET to regulate SERCA2 gene expression in isolated adult rat ventricular myocytes. We find that ET enhances net protein synthesis by ∼40% but significantly downregulates SERCA2 mRNA expression, time dependently, by ∼30–50%, and the expression of SERCA2 protein by ∼ 50%. In myoyctes, ET binds to ETA receptor that couples to Gq and Gi proteins. Inhibition of Gq-PLC-induced phosphoinositide (PI) hydrolysis with U73122 (1 μM) or inhibition of Gi protein with pertussis toxin (PTX) abolishes the ability of ET to downregulate SERCA2 mRNA gene expression. Further investigation suggests that ET coupling to PTX-sensitive Gi with consequent lowering of cAMP is required for downregulation of SERCA2 mRNA levels. Increasing intracellular cAMP quantity using cAMP-specific PDE inhibitor Ro20-1724 or cAMP analog dibutyryl-cAMP reverses ET-induced downregulation of SERCA2 mRNA levels. The data indicate that, in adult myocytes, ET downregulates SERCA2 mRNA and protein levels, and the effect requires cross-talk between Gq and PTX-sensitive Gi pathways.

scholarly journals Red Fluorescent Proteins for Gene Expression and Protein Localization Studies in Streptococcus pneumoniae and Efficient Transformation with DNA Assembled via the Gibson Assembly Method

2015 ◽  
Vol 81 (20) ◽  
pp. 7244-7252 ◽  
Author(s):  
Katrin Beilharz ◽  
Renske van Raaphorst ◽  
Morten Kjos ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Cell Biology ◽  
Fluorescent Proteins ◽  
Protein Localization ◽  
Gibson Assembly ◽  
Content Type ◽  
Assembly Method ◽  
Red Fluorescent Proteins ◽  
Wide Range

ABSTRACTDuring the last decades, a wide range of fluorescent proteins (FPs) have been developed and improved. This has had a great impact on the possibilities in biological imaging and the investigation of cellular processes at the single-cell level. Recently, we have benchmarked a set of green fluorescent proteins (GFPs) and generated a codon-optimized superfolder GFP for efficient use in the important human pathogenStreptococcus pneumoniaeand other low-GC Gram-positive bacteria. In the present work, we constructed and compared four red fluorescent proteins (RFPs) inS. pneumoniae. Two orange-red variants, mOrange2 and TagRFP, and two far-red FPs, mKate2 and mCherry, were codon optimized and examined by fluorescence microscopy and plate reader assays. Notably, protein fusions of the RFPs to FtsZ were constructed by direct transformation of linear Gibson assembly (isothermal assembly) products, a method that speeds up the strain construction process significantly. Our data show that mCherry is the fastest-maturing RFP inS. pneumoniaeand is best suited for studying gene expression, while mKate2 and TagRFP are more stable and are the preferred choices for protein localization studies. The RFPs described here will be useful for cell biology studies that require multicolor labeling inS. pneumoniaeand related organisms.

scholarly journals Use of mCherry Red Fluorescent Protein for Studies of Protein Localization and Gene Expression in Clostridium difficile

2014 ◽  
Vol 81 (5) ◽  
pp. 1652-1660 ◽  
Author(s):  
Eric M. Ransom ◽  
Craig D. Ellermeier ◽  
David S. Weiss
Keyword(s):  
Gene Expression ◽  
Clostridium Difficile ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Protein Localization ◽  
Anaerobic Bacteria ◽  
Gc Content ◽  
Inducible Promoter ◽  
Developed Countries ◽  
Content Type

ABSTRACTFluorescent proteins are powerful reporters in biology, but most require O2for chromophore maturation, making them inherently difficult to use in anaerobic bacteria.Clostridium difficile, a strict anaerobe with a genomic GC content of only 29%, is the leading cause of hospital-acquired diarrhea in developed countries, and new methods for studying this pathogen are sorely needed. We recently demonstrated that a cyan fluorescent protein called CFPoptthat has been codon optimized for production in low-GC bacteria can be used to study protein localization inC. difficileprovided the cells are fixed prior to exposure to air. We describe here a codon-optimized variant of mCherry (mCherryOpt) that exhibits faster acquisition of fluorescence and a better signal-to-noise ratio than CFPopt. We utilizedmCherryOptto construct plasmids for studying protein localization (pRAN473) and gene expression (pDSW1728) inC. difficile. Plasmid pRAN473 is anmCherryOptfusion vector with a tetracycline-inducible promoter. To document its biological utility, we demonstrated septal localization of two cell division proteins, MldA and ZapA. Plasmid pDSW1728 is designed for cloning a promoter of interest upstream ofmCherryOpt. As proof of principle, we studied the expression of thepdaVoperon, which is required for lysozyme resistance. In confirmation and extension of previous reports, we found that expression of thepdaVoperon requires the alternative sigma factor σvand that induction by lysozyme is dose dependent and uniform across the population of lysozyme-treated cells.

scholarly journals The Ferredoxin-Like Protein FerR Regulates PrbP Activity inLiberibacter asiaticus

2018 ◽  
Vol 85 (4) ◽  
Author(s):  
Lei Pan ◽  
Danilo da Silva ◽  
Fernando A. Pagliai ◽  
Natalie A. Harrison ◽  
Claudio F. Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Regulation Of Gene Expression ◽  
Accessory Protein ◽  
Mrna Levels ◽  
Plant Host ◽  
Content Type ◽  
Environmental Signals ◽  
Liberibacter Asiaticus

ABSTRACTInLiberibacter asiaticus, PrbP is an important transcriptional accessory protein that regulates gene expression through interactions with the RNA polymerase β-subunit and a specific sequence on the promoter region. The constitutive expression ofprbPobserved upon chemical inactivation of PrbP-DNA interactionsin vivoindicated that the expression ofprbPwas not autoregulated at the level of transcription. This observation suggested that a modulatory mechanism via protein-protein interactions may be involved.In silicogenome association analysis identified FerR (CLIBASIA_01505), a putative ferredoxin-like protein, as a PrbP-interacting protein. Using a bacterial two-hybrid system and immunoprecipitation assays, interactions between PrbP and FerR were confirmed.In vitrotranscription assays were used to show that FerR can increase the activity of PrbP by 16-fold when present in the PrbP-RNA polymerase reaction mixture. The FerR protein-protein interaction surface was predicted by structural modeling and followed by site-directed mutagenesis. Amino acids V20, V23, and C40 were identified as the most important residues in FerR involved in the modulation of PrbP activityin vitro. The regulatory mechanism of FerR abundance was examined at the transcription level. In contrast toprbPofL. asiaticus(prbPLas), mRNA levels offerRofL. asiaticus(ferRLas) are induced by an increase in osmotic pressure. The results of this study revealed that the activity of the transcriptional activator PrbPLasis modulated via interactions with FerRLas. The induction offerRLasexpression by osmolarity provides insight into the mechanisms of adjusting gene expression in response to host environmental signals inL. asiaticus.IMPORTANCEThe rapid spread and aggressive progression of huanglongbing (HLB) in the major citrus-producing areas have raised global recognition of and vigilance to this disease. As a result, the causative agent,Liberibacter asiaticus, has been investigated from various perspectives. However, gene expression regulatory mechanisms that are important for the survival and persistence of this intracellular pathogen remain largely unexplored. PrbP is a transcriptional accessory protein important forL. asiaticussurvival in the plant host. In this study, we investigated the interactions between PrbP inL. asiaticus(PrbPLas) and a ferredoxin-like protein (FerR) inL. asiaticus, FerRLas. We show that the presence of FerR stabilizes and augments the activity of PrbPLas. In addition, we demonstrate that the expression offerRis induced by increases in osmolarity inLiberibacter crescens. Altogether, these results suggest that FerRLasand PrbPLasmay play important roles in the regulation of gene expression in response to changing environmental signals duringL. asiaticusinfection in the citrus host.

scholarly journals Dynamic Regulation of Mouse Ovarian Stanniocalcin Expression during Gestation and Lactation*

Endocrinology ◽  
2000 ◽  
Vol 141 (9) ◽  
pp. 3412-3421 ◽  
Author(s):  
Harminder K. Deol ◽  
Robin Varghese ◽  
Graham F. Wagner ◽  
Gabriel E. DiMattia
Keyword(s):  
Gene Expression ◽  
Postnatal Development ◽  
Messenger Rna ◽  
Protein Localization ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Glycoprotein Hormone ◽  
Dynamic Regulation ◽  
Functional Relationships ◽  
Mammalian Tissues

Abstract Stanniocalcin is a glycoprotein hormone that appears to play a paracine/autocrine role in several mammalian tissues. Recently studies have shown that stanniocalcin is highly expressed in the ovaries of mice and humans and we have investigated its expression in the mouse ovary during several physiological states to identify potential functional relationships. During postnatal development the pattern of stanniocalcin (STC) gene expression begins to become thecal-restricted as early as day 5 and achieves the adult pattern of expression by two weeks of age. During postnatal development the primary sites of STC protein localization are the theca and oocytes and after maturation it is also strongly concentrated in the corpora lutea. Over the estrous cycle the pattern of both STC gene expression and protein localization do not show dramatic changes though STC immunoreactivity (STCir) staining appears to be greatest during metestrus I. In the superovulation model, however, we observed a significant increase in STC messenger RNA (mRNA) levels after treatment with hCG implying regulation by LH. During gestation the expression of ovarian STC increases 15-fold and is localized to the theca-interstitial cells with lower expression also being found in the corpora lutea. STC also becomes detectable in the serum for the first time suggesting an endocrine role for STC during gestation. Interestingly, the presence of a nursing litter appears to up-regulate STC gene expression in lactating mice suggesting a role for ovarian STC in lactation. Also striking is the intense STCir staining found in oocytes as they are devoid of STC mRNA, thus implying a role for STC in oocyte maturation. Stanniocalcin, to our knowledge, is unique because no other secreted proteins produced by the ovarian thecal-interstitial compartment are significantly induced during mouse pregnancy. In summary, our data provide evidence for the active regulation of STC expression in the ovary during gestation and lactation and therefore implies that STC is a new regulator of the gestational and nursing state.

scholarly journals Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats

2009 ◽  
Vol 37 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Thomas S. Postler ◽  
Murat T. Budak ◽  
Tejvir S. Khurana ◽  
Neal A. Rubinstein
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Protein Localization ◽  
Muscle Growth ◽  
Extraocular Muscles ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Wide Range ◽  
Canonical Pathways

Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone 3,3′,5-triiodo-l-thyronine (T3); subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated control animals. The expression of 468 transcripts was found to be significantly altered, with 466 of these transcripts downregulated in EOMs from T3-treated animals. The biological processes into which the affected genes could be grouped included cellular metabolism, transport, biosynthesis, protein localization, and cell homeostasis. Moreover, 15 distinct biochemical canonical pathways were represented among the genes with altered transcription levels. Strikingly, myostatin ( Gdf8), a potent negative regulator of muscle growth, was found to be strongly downregulated in EOMs from T3-treated animals. Together, these findings suggest that pathological concentrations of thyroid hormone have a unique effect on gene expression in EOMs, which is likely to play a hitherto neglected role in thyroid-associated ophthalmopathies.

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