Erika Galgoczi, Istvan Orsos, Zsanett Molnar, Bernadett Ujhelyi, Zita Steiber, Laszlo Szabo, Beatrix Dienes, Laszlo Csernoch, Endre V Nagy, Monika Katko
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 9, September 2025, Pages 2584–2594
https://doi.org/10.1210/clinem/dgae899
Increased orbital tissue volume due to matrix expansion, orbital fibroblast (OF) proliferation, and adipocyte differentiation are the hallmarks of thyroid eye disease (TED). Their combination with the presence of hyaluronan-bound excess water in the constrains of the bony orbit results in increased intraorbital pressure. High intraorbital pressure, along with changes in the mechanical properties of orbital tissues, may lead to the activation of mechanosensitive receptors. The expression and role of the Piezo1 mechanoreceptor has not been investigated in TED.
We aimed to verify the expression of Piezo1 in OFs, and to study the effect of in vitro Piezo1 activation by its synthetic agonist Yoda1 on adipocyte differentiation.
OF cultures established using orbital connective tissues from patients with TED and controls were studied in the presence or absence of adipogenic stimuli. Piezo1 expression was confirmed by Western Blot and immunofluorescent imaging, and its function was verified by intracellular Ca2+ measurement. Adipogenic differentiation was characterized using Oil Red O staining for lipid accumulation, real-time polymerase chain reaction for gene and Western blot for protein expressions indicative in adipogenesis.
OFs express functional Piezo1 channels. Differentiation into adipocytes is inherent to TED OFs. Piezo1 activation by Yoda1 inhibits the expressions of early (CEBPβ, CEBPδ) and main (PPARγ, CEBPα) transcription factors, and the terminal marker FABP4 during adipogenesis, resulting in markedly lower intracytoplasmic lipid accumulation.
Piezo1 channels are expressed and functional in OFs. Modeling orbital pressure by in vitro Piezo1 activation reduces de novo adipogenesis of OFs derived from TED orbits.
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