{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:47:22Z","timestamp":1788385642665,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Startup Package from the Department of Ophthalmology, School of Medicine, The University of North Carolina at Chapel Hill"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Corneal scarring is a leading cause of blindness. Currently, there is no treatment to prevent and\/or reduce corneal scar formation under pathological conditions. Our previous data showed that the NBL1 protein, also termed the DAN Family BMP (Bone morphogenetic protein) Antagonist, was highly expressed in corneal stromal cells upon wounding. Here, we examined the function of NBL1 in corneal wound healing. Mouse corneas were mechanically wounded, followed by a 2-week treatment using NBL1. Wounded corneas treated with vehicle or an Fc tag served as controls. Compared with the controls, NBL1 treatment facilitated wound re-epithelialization, partially restored the stromal thickness, and significantly reduced corneal scar formation. NBL1 treatment did not decrease immune cell infiltration, indicating that the anti-scarring effect was not dependent on immune suppression. We further examined the anti-fibrotic effect of NBL1 on human corneas. Pairs of human corneas were induced to form myofibroblasts (a key player in fibrosis and scarring) upon wounding and incubation in a medium containing TGF-\u03b21. The OS corneas were treated with Fc as a control, and the OD corneas were treated with NBL1. Compared with the control, human corneas treated with NBL1 had significantly fewer myofibroblasts, which was consistent with these mouse data. A further study revealed that NBL1 treatment inhibited BMP canonical (phospho-Smad1\/5) and no-canonical (phospho-p38) pathways in human corneas. Data show that NBL1 reduced corneal fibrosis and scar formation in mice and cultured human corneas. The underlying molecular mechanism is not certain because both anti-fibrotic Smad1\/5 and pro-fibrotic p38 pathways were inhibited upon NBL1 treatment. Whether the p38 pathway dominates the Smad1\/5 pathway during corneal fibrosis, leading to the anti-fibrotic effect of NBL1, needs further investigation.<\/jats:p>","DOI":"10.3390\/biom13111570","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:28:25Z","timestamp":1698128905000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8379-5117","authenticated-orcid":false,"given":"Chi-Hao","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystal Lynn","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Cell Biology and Physiology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.exer.2014.02.007","article-title":"Wounding the cornea to learn how it heals","volume":"121","author":"Stepp","year":"2014","journal-title":"Exp. 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