{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:50:42Z","timestamp":1782762642462,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis, and dysregulation of the transforming growth factor-beta (TGF-\u03b2) signaling pathways contributes to retinal fibrosis and inflammatory diseases, including proliferative vitreoretinopathy (PVR). Tacrolimus (FK506), an immunosuppressant, has shown potential antifibrotic properties, but its effects on TGF-\u03b2-related genes and microRNAs (miRNAs) in RPE cells remain unclear. Human RPE (H-RPE) cells were treated with lipopolysaccharide (LPS) to induce inflammation and subsequently exposed to tacrolimus. Gene and miRNA expression profiling related to TGF-\u03b2 signaling pathways were conducted using microarrays, followed by Quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR) validation. Protein levels were assessed via enzyme-linked immunosorbent assay (ELISA), and interactions were analyzed using STRING database network analysis. Tacrolimus modulated key components of the TGF-\u03b2 pathway, upregulating TGF-\u03b22, TGF-\u03b23, SMAD2, and SMAD4 while downregulating TGF-\u03b2R1 and SMAD7. JAK\/STAT and MAPK pathways were also affected, indicating broad regulatory effects. miRNA profiling identified hsa-miR-200a-3p, hsa-miR-589-3p, hsa-miR-21, and hsa-miR-27a-5p as key regulators. STRING analysis confirmed strong functional interactions within the TGF-\u03b2 network. In conclusion, tacrolimus modulates both canonical (upregulation of SMAD2\/4 and downregulation of SMAD7) and non-canonical (JAK\/STAT and MAPK) TGF-\u03b2 signaling pathways in LPS-stimulated RPE cells. These changes collectively suggest a dual anti-inflammatory and anti-fibrotic effect. The increased TGF-\u03b22 and decreased SMAD7 levels, alongside altered miRNA expression (e.g., downregulation of miR-200a-3p), indicate that tacrolimus may inhibit key profibrotic mechanisms underlying PVR. These findings support the potential therapeutic repurposing of tacrolimus in PVR and warrant further in vivo validation.<\/jats:p>","DOI":"10.3390\/ijms26115402","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T11:14:12Z","timestamp":1749035652000},"page":"5402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tacrolimus Modulates TGF-\u03b2 Signaling\u2013Related Genes and MicroRNAs in Human Retinal Pigment Epithelial Cells Activated by Lipopolysaccharide"],"prefix":"10.3390","volume":"26","author":[{"given":"Aleksandra","family":"Kie\u0142basi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Opthalmology, University Clinical Center Named After Prof. K. Gibi\u0144ski of the Medical University of Silesia in Katowice, 40-514 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-5391","authenticated-orcid":false,"given":"Katarzyna","family":"Krysik","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, St. Barbara Hospital, Trauma Centre, 41-200 Sosnowiec, Poland"},{"name":"Department of Ophthalmology, Faculty of Medicine, Academy of Silesia, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Janiszewska-Bil","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, St. Barbara Hospital, Trauma Centre, 41-200 Sosnowiec, Poland"},{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Machaj","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, St. Barbara Hospital, Trauma Centre, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-7747","authenticated-orcid":false,"given":"Zuzanna","family":"Lelek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, St. Barbara Hospital, Trauma Centre, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Su\u0142kowska","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Nawotny-Czupryna","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-7145","authenticated-orcid":false,"given":"Beniamin Oskar","family":"Grabarek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Markitantova, Y., and Simirskii, V. 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