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

English version

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

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

Souhrn

Klíčová slova:

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