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Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor


Autoři: Christine L. Hammond aff001;  Elisa Roztocil aff001;  Richard P. Phipps aff002;  Steven E. Feldon aff001;  Collynn F. Woeller aff001
Působiště autorů: Flaum Eye Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New York, United States of America aff001;  Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222779

Souhrn

Thyroid eye disease (TED) can lead to scar formation and tissue remodeling in the orbital space. In severe cases, the scarring process leads to sight-threatening pathophysiology. There is no known effective way to prevent scar formation in TED patients, or to reverse scarring once it occurs. In this study, we show that the proton pump inhibitors (PPIs), esomeprazole and lansoprazole, can prevent transforming growth factor beta (TGFβ)-mediated differentiation of TED orbital fibroblasts to myofibroblasts, a critical step in scar formation. Both PPIs prevent TGFβ-induced increases in alpha-smooth muscle actin (αSMA), calponin, and collagen production and reduce TED orbital fibroblast cell proliferation and migration. Esomeprazole and lansoprazole exert these effects through an aryl hydrocarbon receptor (AHR)-dependent pathway that includes reducing β-catenin/Wnt signaling. We conclude that PPIs are potentially useful therapies for preventing or treating TED by reducing the myofibroblast accumulation that occurs in the disease.

Klíčová slova:

Biology and life sciences – Cell biology – Genetics – Gene expression – Biochemistry – Nucleic acids – Research and analysis methods – Proteins – Molecular biology – Gene regulation – Molecular biology techniques – Cellular types – Animal cells – Anatomy – Medicine and health sciences – Small interfering RNAs – RNA – Non-coding RNA – Molecular biology assays and analysis techniques – Gene expression and vector techniques – Connective tissue cells – Fibroblasts – Biological tissue – Connective tissue – Collagens – Signal transduction – Protein expression – Specimen preparation and treatment – Staining – Cell signaling – Signaling cascades – Wnt signaling cascade – Post-translational modification – TGF-beta signaling cascade – Phosphorylation – Nuclear staining – DAPI staining


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