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They play an essential role in maintaining corneal physiological function. Studying the factors that affect the phenotype and behavior of keratocytes offers meaningful perspectives for improving the understanding and treatment of corneal injuries. In this study, 3% strain was applied to human keratocytes using the Flexcell\u00ae Tension Systems. Real\u2010time quantitative PCR (RT\u2010qPCR) and western blot were used to investigate the influence of strain on the expression of intracellular aldehyde dehydrogenase 3A1 (ALDH3A1). ALDH3A1 knockdown was achieved using double\u2010stranded RNA\u2010mediated interference (RNAi). Immunofluorescence (IF) staining was employed to observe the impact of changes in ALDH3A1 expression on nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) nuclear translocation. Keratocyte proliferation and migration were assessed by bromodeoxyuridine (BrdU) assay and scratch wound healing assay, respectively. Mouse injury models and single\u2010cell RNA sequencing of keratocytes from keratoconus patients were used to assess how strain influenced ALDH3A1 in\u00a0vivo. Our results demonstrate that 3% strain suppresses keratocyte proliferation and increases ALDH3A1. Increased ALDH3A1 inhibits NF\u2010\u03baB nuclear translocation, a key step in the activation of the NF\u2010\u03baB signaling pathway. Conversely, ALDH3A1 knockdown promotes NF\u2010\u03baB nuclear translocation, ultimately enhancing keratocyte proliferation and migration. Elevated ALDH3A1 levels were also observed in mouse injury models with increased corneal strain and keratoconus patients. These findings provide valuable insights for further research into the role of corneal strain and its connection to corneal injury repair.<\/jats:p>","DOI":"10.1096\/fj.202401392r","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T10:45:31Z","timestamp":1733741131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Corneal strain influences keratocyte proliferation and migration through upregulation of\n                    <scp>ALDH3A1<\/scp>\n                    expression"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3150-5884","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical and Translational Biology Ume\u00e5 University  Ume\u00e5 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