@article{MTMT:34069251,
	title = {Sigma-1 Receptor Agonist Fluvoxamine Ameliorates Fibrotic Response of Trabecular Meshwork Cells},
	url = {https://m2.mtmt.hu/api/publication/34069251},
	author = {Hodrea, Judit and Tran, Ngoc Minh and Besztercei, Balázs and Medveczki, Tímea and Szabó, Attila and Őrfi, László and Kovács, Illés and Fekete, Andrea},
	doi = {10.3390/ijms241411646},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34069251},
	issn = {1661-6596},
	abstract = {Primary open-angle glaucoma remains a global issue, lacking a definitive treatment. Increased intraocular pressure (IOP) is considered the primary risk factor of the disease and it can be caused by fibrotic-like changes in the trabecular meshwork (TM) such as increased tissue stiffness and outflow resistance. Previously, we demonstrated that the sigma-1 receptor (S1R) agonist fluvoxamine (FLU) has anti-fibrotic properties in the kidney and lung. In this study, the localization of the S1R in TM cells was determined, and the anti-fibrotic efficacy of FLU was examined in both mouse and human TM cells. Treatment with FLU reduced the F-actin rearrangement, inhibited cell proliferation and migration induced by the platelet-derived growth factor and decreased the levels of fibrotic proteins. The protective role of the S1R in fibrosis was confirmed by a more pronounced increase in alpha smooth muscle actin and F-actin bundle and clump formation in primary mouse S1R knockout TM cells. Furthermore, FLU demonstrated its protective effects by increasing the production of nitric oxide and facilitating the degradation of the extracellular matrix through the elevation of cathepsin K. These findings suggest that the S1R could be a novel target for the development of anti-fibrotic drugs and offer a new therapeutic approach for glaucoma.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Hodrea, Judit/0000-0002-6388-4021; Tran, Ngoc Minh/0000-0002-6925-0871; Besztercei, Balázs/0000-0002-5636-284X; Medveczki, Tímea/0000-0002-3618-6690; Szabó, Attila/0000-0001-7321-9861; Őrfi, László/0000-0001-6149-2385; Kovács, Illés/0000-0001-5763-0482; Fekete, Andrea/0000-0002-0210-153X}
}

@article{MTMT:34069454,
	title = {Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells},
	url = {https://m2.mtmt.hu/api/publication/34069454},
	author = {Tran, Ngoc Minh and Medveczki, Tímea and Besztercei, Balázs and Török, György and Szabó, Attila and Gasull, Xavier and Kovács, Illés and Fekete, Andrea and Hodrea, Judit},
	doi = {10.3390/life13071581},
	journal-iso = {LIFE-BASEL},
	journal = {LIFE-BASEL},
	volume = {13},
	unique-id = {34069454},
	abstract = {The trabecular meshwork (TM) route is the principal outflow egress of the aqueous humor. Actin cytoskeletal remodeling in the TM and extracellular matrix (ECM) deposition increase TM stiffness, outflow resistance, and elevate intraocular pressure (IOP). These alterations are strongly linked to transforming growth factor-β2 (TGFβ2), a known profibrotic cytokine that is markedly elevated in the aqueous humor of glaucomatous eyes. Sigma-1 receptor (S1R) has been shown to have neuroprotective effects in the retina, but data are lacking about its role in the TM. In this study, we identified the presence of S1R in mouse TM tissue and investigated the effect of an S1R agonist fluvoxamine (FLU) on TGFβ2-induced human TM cells regarding cell proliferation; ECM-related functions, including F-actin reorganization; and the accumulation of ECM elements. TGFβ2 increased the proliferation, cytoskeletal remodeling, and protein levels of fibronectin, collagen type IV, and connective tissue growth factor, and decreased the level of matrix metalloproteinase-2. Most importantly, FLU reversed all these effects of TGFβ2, suggesting that S1R agonists could be potential candidates for preserving TM function and thus maintaining normal IOP.},
	year = {2023},
	eissn = {2075-1729},
	orcid-numbers = {Tran, Ngoc Minh/0000-0002-6925-0871; Medveczki, Tímea/0000-0002-3618-6690; Besztercei, Balázs/0000-0002-5636-284X; Török, György/0000-0001-7616-5782; Szabó, Attila/0000-0001-7321-9861; Gasull, Xavier/0000-0002-6154-8323; Kovács, Illés/0000-0001-5763-0482; Fekete, Andrea/0000-0002-0210-153X; Hodrea, Judit/0000-0002-6388-4021}
}

@article{MTMT:3049309,
	title = {Sigma1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury},
	url = {https://m2.mtmt.hu/api/publication/3049309},
	author = {Hosszú, Ádám and Antal, Zsuzsanna and Lénárt, Lilla and Hodrea, Judit and Kőszegi, Sándor and Balogh, Dóra Bianka and Bánki, Nóra Fanni and Wágner, László József and Dénes, Ádám and Hamar, Péter and Degrell, P and Vannay, Ádám and Szabó, Attila and Fekete, Andrea},
	doi = {10.1681/ASN.2015070772},
	journal-iso = {J AM SOC NEPHROL},
	journal = {JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY},
	volume = {28},
	unique-id = {3049309},
	issn = {1046-6673},
	abstract = {Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role ofsigma1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinitysigma1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused thesigma1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked bysigma1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney,sigma1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by thesigma1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury,sigma1-receptor agonists improved postischemic survival and renal functionviaactivation of Akt-mediated nitric oxide signaling in the kidney. Thus,sigma1-receptor activation might provide a therapeutic option for renoprotective therapy.},
	year = {2017},
	eissn = {1533-3450},
	pages = {152-165},
	orcid-numbers = {Hosszú, Ádám/0000-0002-8415-5637; Antal, Zsuzsanna/0000-0003-2003-6564; Lénárt, Lilla/0000-0001-5948-7990; Hodrea, Judit/0000-0002-6388-4021; Kőszegi, Sándor/0000-0003-2542-7871; Balogh, Dóra Bianka/0000-0001-6554-2634; Bánki, Nóra Fanni/0000-0002-4327-4314; Wágner, László József/0000-0001-6806-4076; Hamar, Péter/0000-0002-1095-3564; Vannay, Ádám/0000-0001-7412-4733; Szabó, Attila/0000-0001-7321-9861; Fekete, Andrea/0000-0002-0210-153X}
}