TY - JOUR AU - Galgóczi, Erika AU - Orsos, Istvan AU - Molnar, Zsanett AU - Ujhelyi, Bernadett AU - Steiber, Zita AU - Szabó, László AU - Dienes, Beatrix AU - Csernoch, László AU - Nagy, Endre AU - Katkó, Mónika TI - Stimulation of Piezo1 Mechanosensitive Channels Inhibits Adipogenesis in Thyroid Eye Disease JF - JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM J2 - J CLIN ENDOCR METAB PY - 2025 PG - 11 SN - 0021-972X DO - 10.1210/clinem/dgae899 UR - https://m2.mtmt.hu/api/publication/35697929 ID - 35697929 N1 - Corrected proof AB - Context: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Fruzsina Réka AU - Katkó, Mónika AU - Csiki, Róbert AU - Galgóczi, Erika AU - Molnar, Zsanett AU - Erdei, Annamária AU - Bodor, Miklós AU - Steiber, Zita AU - Ujhelyi, Bernadett AU - Nagy, Endre TI - Characteristics of Hyaluronan Metabolism During Myofibroblast Differentiation in Orbital Fibroblasts JF - INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE J2 - INVEST OPHTH VIS SCI VL - 65 PY - 2024 IS - 13 PG - 12 SN - 0146-0404 DO - 10.1167/iovs.65.13.13 UR - https://m2.mtmt.hu/api/publication/35620179 ID - 35620179 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [K143464]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [K_22] Funding text: Supported by a grant from the Hungarian National Research, Development and Innovation Office (K143464) . Project K143464 has been implemented with support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund (K_22) . AB - PURPOSE. To study the impact of myofibroblast differentiation (MD) on hyaluronan (HA) turnover in orbital fibroblasts (OFs) focusing on the expression of its key enzymes and their potential implications in the pathogenesis of thyroid eye disease (TED). METHODS. Primary cultures of OFs were established from tissue samples (TED OFs, n = 4; non-TED OFs, n = 5). MD was induced by TGF-β1 (5 ng/mL). Measurements were performed after 24- and 72-hour treatments. The proliferation rate was determined by 5-bromo-2 -deoxyuridine (BrdU) incorporation. HA level and size were measured using an aggrecan-based ELISA-like method and agarose gel electrophoresis, respectively. mRNA expressions of myofibroblast markers and enzymes with a role in HA metabolism were determined using real-time PCR. RESULTS. Upregulation of type I collagen alpha1 chain, alpha-smooth muscle actin, and fibronectin indicated that OFs underwent MD after stimulation by TGF-β. After 72 hours, proliferation of untreated cultures declined, but it remained higher in myofibroblasts. Pericellular HA content, but not HA in the supernatant of myofibroblasts, increased compared to untreated cells. TGF-β was a potent stimulator of hyaluronan synthase 1 (HAS1) expression. The expression of hyaluronidase-1 and cell migration–inducing protein (CEMIP) diminished following MD, whereas the expression of transmembrane protein 2, the regulator of HA catabolism through CEMIP, was elevated. The size distribution of HA shifted toward a high-molecular-weight form following treatment with TGF-β. CONCLUSIONS. OFs undergoing MD are characterized by decreased HA turnover as a consequence of the inhibition of hyaluronidases and HAS1 induction. Our results suggest that hyaluronidases could be potential targets in the treatment of TED. LA - English DB - MTMT ER - TY - JOUR AU - Csiki, Róbert AU - Papp, Fruzsina Réka AU - Galgóczi, Erika AU - Steiber, Zita AU - Ujhelyi, Bernadett AU - Nagy, Endre AU - Katkó, Mónika TI - Production of chemerin by orbital fibroblasts during myofibroblast and adipocyte differentiation JF - ENDOCRINE ABSTRACTS J2 - ENDOCR ABSTR VL - 101 PY - 2024 SN - 1470-3947 DO - 10.1530/endoabs.101.PS1-01-04 UR - https://m2.mtmt.hu/api/publication/35486694 ID - 35486694 LA - English DB - MTMT ER - TY - JOUR AU - Papp, Fruzsina Réka AU - Csiki, Róbert AU - Katkó, Mónika AU - Galgóczi, Erika AU - Steiber, Zita AU - Ujhelyi, Bernadett AU - Nagy, Endre TI - Characteristics of hyaluronan metabolism during myofibroblast differentiation in orbital fibroblasts JF - ENDOCRINE ABSTRACTS J2 - ENDOCR ABSTR VL - 101 PY - 2024 SN - 1470-3947 DO - 10.1530/endoabs.101.OP-07-03 UR - https://m2.mtmt.hu/api/publication/35486686 ID - 35486686 LA - English DB - MTMT ER - TY - JOUR AU - Galgóczi, Erika AU - Orsos, Istvan AU - Molnar, Zsanett AU - Ujhelyi, Bernadett AU - Steiber, Zita AU - Szabó, László AU - Dienes, Beatrix AU - Csernoch, László AU - Nagy, Endre AU - Katkó, Mónika TI - Modelling of mechanical stimuli through piezo1 receptor activation and its effect on adipogenic differentiation of orbital fibroblasts JF - ENDOCRINE ABSTRACTS J2 - ENDOCR ABSTR VL - 101 PY - 2024 PG - 1 SN - 1470-3947 DO - 10.1530/endoabs.101.PS1-01-01 UR - https://m2.mtmt.hu/api/publication/35195783 ID - 35195783 LA - English DB - MTMT ER - TY - JOUR AU - Galgóczi, Erika AU - Molnar, Zsanett AU - Katkó, Mónika AU - Ujhelyi, Bernadett AU - Steiber, Zita AU - Nagy, Endre TI - Cyclosporin A inhibits PDGF-BB induced hyaluronan synthesis in orbital fibroblasts JF - CHEMICO-BIOLOGICAL INTERACTIONS J2 - CHEM-BIOL INTERACT VL - 396 PY - 2024 SP - 111045 SN - 0009-2797 DO - 10.1016/j.cbi.2024.111045 UR - https://m2.mtmt.hu/api/publication/34866147 ID - 34866147 LA - English DB - MTMT ER - TY - BOOK AU - Fodor, Mariann AU - Takács, Lili AU - Kettesy, Andrea Beáta AU - Kolozsvári, Bence Lajos AU - Nagy, Annamária AU - Steiber, Zita AU - Pásztor, Dorottya AU - Surányi, Éva AU - Széll, Noémi AU - Beáta, Bajdik AU - Balla, Szabolcs AU - Aranyosi, János AU - Mátyás, Hankovszky AU - Sára, Makhoul AU - Dorottya, Lilla Nagy AU - Orsolya, Pásztor AU - Anett, Porempovics AU - Ujhelyi, Bernadett TI - Ophthalmogy Practice Notes PB - Debreceni Egyetem CY - Debrecen PY - 2023 UR - https://m2.mtmt.hu/api/publication/34323209 ID - 34323209 LA - English DB - MTMT ER - TY - JOUR AU - Galgóczi, Erika AU - Katkó, Mónika AU - Papp, Fruzsina Réka AU - Csiki, Róbert AU - Bak-Csiha, Sára AU - Erdei, Annamária AU - Bodor, Miklós AU - Ujhelyi, Bernadett AU - Steiber, Zita AU - Győry, Ferenc AU - Nagy, Endre TI - Glucocorticoids Directly Affect Hyaluronan Production of Orbital Fibroblasts; A Potential Pleiotropic Effect in Graves’ Orbitopathy JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 1 SN - 1431-5157 DO - 10.3390/molecules28010015 UR - https://m2.mtmt.hu/api/publication/33578444 ID - 33578444 AB - Orbital connective tissue expansion is a hallmark of Graves’ orbitopathy (GO). In moderate-to-severe active GO, glucocorticoids (GC) are the first line of treatment. Here we show that hydrocortisone (HC), prednisolone (P), methylprednisolone (MP), and dexamethasone (DEX) inhibit the hyaluronan (HA) production of orbital (OF) and dermal (DF) fibroblasts. HA production of GO OFs (n = 4), NON-GO OFs (n = 4) and DFs (n = 4) was measured by ELISA. mRNA expression of enzymes of HA metabolism and fibroblast proliferation was examined by RT-PCR and BrdU incorporation, respectively. After 24 h of GC treatment (1µM) HA production decreased by an average of 67.9 ± 3.11% (p < 0.0001) in all cell cultures. HAS2, HAS3 and HYAL1 expression in OFs also decreased (p = 0.009, p = 0.0005 and p = 0.015, respectively). Ten ng/mL PDGF-BB increased HA production and fibroblast proliferation in all cell lines (p < 0.0001); GC treatment remained effective and reduced HA production under PDGF-BB-stimulated conditions (p < 0.0001). MP and DEX reduced (p < 0.001, p = 0.002, respectively) PDGF-BB-induced HAS2 expression in OFs. MP and DEX treatment decreased PDGF-BB stimulated HAS3 expression (p = 0.035 and p = 0.029, respectively). None of the GCs tested reduced the PDGF-BB stimulated proliferation rate. Our results confirm that GCs directly reduce the HA production of OFs, which may contribute to the beneficial effect of GCs in GO. LA - English DB - MTMT ER - TY - JOUR AU - Galgóczi, Erika AU - Katko, Monika AU - Erdei, Annamária AU - Bodor, Miklós AU - Ujhelyi, Bernadett AU - Steiber, Zita AU - Győry, Ferenc AU - Nagy, Endre TI - The effect of glucocorticoids on hyaluronan production of orbital fibroblasts JF - ENDOCRINE ABSTRACTS J2 - ENDOCR ABSTR VL - 84 PY - 2022 SN - 1470-3947 DO - 10.1530/endoabs.84.PS2-07-64 UR - https://m2.mtmt.hu/api/publication/33211389 ID - 33211389 LA - English DB - MTMT ER - TY - JOUR AU - Erdei, Annamária AU - Gazdag, Annamária AU - Ujhelyi, Bernadett AU - Nagy, Edit B AU - Berényi, Ervin László AU - Berta, Eszter AU - Steiber, Zita AU - Barna, Sándor Kristóf AU - Mezősi, Emese AU - Bodor, Miklós AU - Nagy, Endre TI - Non-surgical orbital decompression using diuresis in dysthyroid optic neuropathy: a case report JF - EUROPEAN THYROID JOURNAL J2 - EUR THYROID J VL - 11 PY - 2022 IS - 5 PG - 5 SN - 2235-0640 DO - 10.1530/ETJ-22-0078 UR - https://m2.mtmt.hu/api/publication/33032320 ID - 33032320 AB - Dysthyroid optic neuropathy (DON) is a rare, severe form of thyroid eye disease, in which decreased visual acuity is accompanied by characteristic MRI findings. The treatment of DON has always been a challenge.In a patient in whom visual acuity deteriorated on the left eye, mannitol 20% 200 ml followed by furosemide 40 mg 6 hours later, administered daily, were initiated on the day of admission. Visual function by ophthalmology methods, and orbital compartment volumes and water content by MRI were followed. Intravenous diuretics resulted in immediate therapeutic response. Visual acuity improved from 20/50 to 20/25 after two days of treatment. MRI revealed decreasing water content of both the muscle and connective tissue compartments without any volume changes. Subsequently, corticosteroids and orbital irradiation were started. Orbital decompression surgery was not required.Edematous swelling of orbital tissues is an established contributor of local pressure increase in thyroid eye disease. Diuretics reduce orbital pressure and, if confirmed by others, may be useful additions to the standard of care in sight threatening DON. LA - English DB - MTMT ER -