{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:47:31Z","timestamp":1781333251813,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UConn Health Biomedical Engineering Department Startup Funds","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry Eye Disease (DED) is a complex pathology affecting millions of people with significant impact on quality of life. Corneal inflammation, including via the nuclear factor kappa B (NF\u03baB) pathway, plays a key etiological role in DED. Recombinant human proteoglycan 4 (rhPRG4) has been shown to be a clinically effective treatment for DED that has anti-inflammatory effects in corneal epithelial cells, but the underlying mechanism is still not understood. Our goal was to understand if rhPRG4 affects tumor necrosis factor \u03b1 (TNF\u03b1)-stimulated inflammatory activity in corneal epithelial cells. We treated hTERT-immortalized corneal epithelial (hTCEpi) cells \u00b1 TNF\u03b1 \u00b1 rhPRG4 and performed Western blotting on cell lysate and RNA sequencing. Bioinformatics analysis revealed that rhPRG4 had a significant effect on TNF\u03b1-mediated inflammation with potential effects on matricellular homeostasis. rhPRG4 reduced activation of key inflammatory pathways and decreased expression of transcripts for key inflammatory cytokines, interferons, interleukins, and transcription factors. TNF\u03b1 treatment significantly increased phosphorylation and nuclear translocation of p65, and rhPRG4 significantly reduced both these effects. RNA sequencing identified human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), a ubiquitin-like modifier protein which has not been studied in the context of DED, as a key pro-inflammatory transcript increased by TNF\u03b1 and decreased by rhPRG4. These results were confirmed at the protein level. In summary, rhPRG4 is able to downregulate NF\u03baB activity in hTCEpi cells, suggesting a potential biological mechanism by which it may act as a therapeutic for DED.<\/jats:p>","DOI":"10.3390\/ijms232112711","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:40:36Z","timestamp":1666586436000},"page":"12711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNF\u03b1-Stimulated NF\u03baB Activity and FAT10 Expression in Human Corneal Epithelial Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Nikhil G.","family":"Menon","sequence":"first","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-9738","authenticated-orcid":false,"given":"Yasir","family":"Suhail","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Goyal","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Du","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Tanguay","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Jay","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"},{"name":"School of Engineering, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallika","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4241-9427","authenticated-orcid":false,"family":"Kshitiz","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-254X","authenticated-orcid":false,"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jtos.2017.08.003","article-title":"TFOS DEWS II Report Executive Summary","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. 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