{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:28Z","timestamp":1782279988276,"version":"3.54.5"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetic keratopathy constitutes a prevalent ocular complication of diabetes mellitus, clinically manifested as delayed corneal epithelial repair, recurrent epithelial defects, and potential corneal ulceration. Currently, the underlying molecular mechanisms and effective therapeutic strategies remain incompletely defined. This study integrates transcriptomic analysis with computational pharmacology and experimental validation. The results suggest that ELF3 is associated with corneal epithelial senescence in diabetes and identify IL-2 as a potential modulator of ELF3-associated signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analysis of Gene Expression Omnibus (GEO) datasets, combined with transcription factor enrichment, was performed to identify principal transcriptional regulators. In human corneal epithelial cells (HCECs) stimulated with high glucose, EdU assays, wound-healing assays, senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) staining, and Western blotting were employed to assess HCEC proliferation, migration, and senescence. Following siRNA-mediated ELF3 knockdown or plasmid-driven overexpression, phenotypic and protein-level changes were evaluated. Transcriptome-guided drug prediction and molecular docking were performed to identify candidate ELF3 modulators. Pathways associated with ELF3 were screened\n                      <jats:italic>via<\/jats:italic>\n                      RNA sequencing and subsequently validated by Western blotting. A type 1 diabetic mouse model was established using streptozotocin (STZ). The therapeutic efficacy of IL-2 on corneal senescence in diabetic mice was assessed using immunohistochemistry, SA-\u03b2-gal staining, and sodium fluorescein staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analysis identified ELF3 as a critical transcription factor associated with diabetic keratopathy. In HCECs under high-glucose conditions, ELF3 expression was significantly upregulated, coinciding with reduced proliferation, impaired migration, and accelerated senescence. ELF3 knockdown attenuated these impairments, whereas its overexpression exacerbated them. Drug prediction and molecular docking identified IL-2 as a potential modulator of ELF3-associated signaling. RNA sequencing analysis indicated that the NF-\u03baB pathway is associated with ELF3-mediated regulation of cellular senescence.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , IL-2 downregulated ELF3 expression, suppressing the NF-\u03baB pathway and attenuating cellular senescence. In diabetic mice, topical IL-2 application reduced ELF3 levels, decreased senescence markers, and accelerated corneal epithelial wound healing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings establish ELF3 as a critical driver of hyperglycemia-induced corneal epithelial senescence. IL-2 attenuates senescence and promotes corneal wound healing while suppressing ELF3-associated signaling and NF-\u03baB pathway activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1812782","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:32Z","timestamp":1782276572000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ELF3 promotes hyperglycemia-induced corneal epithelial senescence and IL-2 attenuates ELF3-associated signaling"],"prefix":"10.3389","volume":"13","author":[{"given":"Sujun","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, The First Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jtos.2023.07.008","article-title":"Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption","volume":"30","author":"Abu-Romman","year":"2023","journal-title":"Ocul. 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