{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T14:17:56Z","timestamp":1793456276659,"version":"4.5.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171024"],"award-info":[{"award-number":["82171024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal inflammation in a mouse model of benzalkonium chloride (BAC)-induced dry eye and the TNF-\u03b1-induced NF-\u03baB signaling pathway in human corneal epithelial cells (HCECs). A mouse model of dry eye was established by administering with BAC to BALB\/c mice, and the expression of TNF-\u03b1, IL-1\u03b2, IL-6, IL-8, cyclooxygenase 2 (COX2), interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) in the corneas of dry eye model mice was significantly increased; this was accompanied by the upregulation of miR-146a and activation of the NF-\u03baB pathway. In vitro, TNF-\u03b1 induced miR-146a expression in HCECs, while the NF-\u03baB inhibitor SC-514 reduced the expression of miR-146a. Overexpression of miR-146a decreased the expression of IRAK1 and TRAF6, which have been identified as targets of miR-146a. Furthermore, overexpression of miR-146a suppressed NF-\u03baB p65 translocation from the cytoplasm to the nucleus. Moreover, overexpression of miR-146a attenuated the TNF-\u03b1-induced expression of IL-6, IL-8, COX2 and intercellular adhesion molecule 1 (ICAM1), while inhibition of miR-146a exerted the opposite effect. Our results suggest that miR-146a mediates the inflammatory response in DED. MiR-146a negatively regulates inflammation in HCECs through the IRAK1\/TRAF6\/NF-\u03baB pathway, and this may serve as a potential therapeutic approach for the treatment of DED.<\/jats:p>","DOI":"10.1038\/s41598-023-38367-4","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T10:02:30Z","timestamp":1689069750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["MicroRNA-146a negatively regulates inflammation via the IRAK1\/TRAF6\/NF-\u03baB signaling pathway in dry eye"],"prefix":"10.1038","volume":"13","author":[{"given":"Ruifang","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,11]]},"reference":[{"key":"38367_CR1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","volume":"15","author":"JP Craig","year":"2017","unstructured":"Craig, J. P. et al. TFOS DEWS II definition and classification report. Ocul. Surf. 15, 276\u2013283. https:\/\/doi.org\/10.1016\/j.jtos.2017.05.008 (2017).","journal-title":"Ocul. Surf."},{"key":"38367_CR2","doi-asserted-by":"publisher","first-page":"DES7","DOI":"10.1167\/iovs.17-23475","volume":"59","author":"J Shimazaki","year":"2018","unstructured":"Shimazaki, J. Definition and diagnostic criteria of dry eye disease: Historical overview and future directions. Investig. Ophthalmol. Vis. Sci. 59, DES7\u2013DES12. https:\/\/doi.org\/10.1167\/iovs.17-23475 (2018).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"38367_CR3","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/icu.0000000000000569","volume":"30","author":"EC O'Neil","year":"2019","unstructured":"O\u2019Neil, E. C., Henderson, M., Massaro-Giordano, M. & Bunya, V. Y. Advances in dry eye disease treatment. Curr. Opin. Ophthalmol. 30, 166\u2013178. https:\/\/doi.org\/10.1097\/icu.0000000000000569 (2019).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"38367_CR4","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1016\/j.ophtha.2017.08.029","volume":"124","author":"MK Rhee","year":"2017","unstructured":"Rhee, M. K. & Mah, F. S. Inflammation in dry eye disease: How do we break the cycle?. Ophthalmology 124, S14-s19. https:\/\/doi.org\/10.1016\/j.ophtha.2017.08.029 (2017).","journal-title":"Ophthalmology"},{"key":"38367_CR5","doi-asserted-by":"publisher","first-page":"DES192","DOI":"10.1167\/iovs.17-23651","volume":"59","author":"T Yamaguchi","year":"2018","unstructured":"Yamaguchi, T. Inflammatory response in dry eye. Investig. Ophthalmol. Vis. Sci. 59, DES192\u2013DES199. https:\/\/doi.org\/10.1167\/iovs.17-23651 (2018).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"38367_CR6","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1089\/jir.2018.0155","volume":"39","author":"G Mahesh","year":"2019","unstructured":"Mahesh, G. & Biswas, R. MicroRNA-155: A master regulator of inflammation. J. Interferon Cytokine Res. 39, 321\u2013330. https:\/\/doi.org\/10.1089\/jir.2018.0155 (2019).","journal-title":"J. Interferon Cytokine Res."},{"key":"38367_CR7","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.canlet.2019.02.051","volume":"451","author":"J Jeffries","year":"2019","unstructured":"Jeffries, J., Zhou, W., Hsu, A. Y. & Deng, Q. miRNA-223 at the crossroads of inflammation and cancer. Cancer Lett. 451, 136\u2013141. https:\/\/doi.org\/10.1016\/j.canlet.2019.02.051 (2019).","journal-title":"Cancer Lett."},{"key":"38367_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10715762.2020.1852234","volume":"55","author":"J Yan","year":"2021","unstructured":"Yan, J. et al. MicroRNA-217 modulates inflammation, oxidative stress, and lung injury in septic mice via SIRT1. Free Radic. Res. 55, 1\u201310. https:\/\/doi.org\/10.1080\/10715762.2020.1852234 (2021).","journal-title":"Free Radic. Res."},{"key":"38367_CR9","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/nature03315","volume":"433","author":"LP Lim","year":"2005","unstructured":"Lim, L. P. et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769\u2013773. https:\/\/doi.org\/10.1038\/nature03315 (2005).","journal-title":"Nature"},{"key":"38367_CR10","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nrg2290","volume":"9","author":"W Filipowicz","year":"2008","unstructured":"Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight?. Nat. Rev. Genet. 9, 102\u2013114. https:\/\/doi.org\/10.1038\/nrg2290 (2008).","journal-title":"Nat. Rev. Genet."},{"key":"38367_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17071076","author":"Y Chen","year":"2016","unstructured":"Chen, Y. et al. MicroRNA-146a-5p negatively regulates pro-inflammatory cytokine secretion and cell activation in lipopolysaccharide stimulated human hepatic stellate cells through inhibition of toll-like receptor 4 signaling pathways. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms17071076 (2016).","journal-title":"Int. J. Mol. Sci."},{"key":"38367_CR12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/tox.22561","volume":"33","author":"L Liu","year":"2018","unstructured":"Liu, L. et al. MiR-146a regulates PM(1)-induced inflammation via NF-\u03baB signaling pathway in BEAS-2B cells. Environ. Toxicol. 33, 743\u2013751. https:\/\/doi.org\/10.1002\/tox.22561 (2018).","journal-title":"Environ. Toxicol."},{"key":"38367_CR13","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1038\/jid.2014.89","volume":"134","author":"F Meisgen","year":"2014","unstructured":"Meisgen, F. et al. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J. Investig. Dermatol. 134, 1931\u20131940. https:\/\/doi.org\/10.1038\/jid.2014.89 (2014).","journal-title":"J. Investig. Dermatol."},{"key":"38367_CR14","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1261\/rna.071985.119","volume":"26","author":"Y Fei","year":"2020","unstructured":"Fei, Y. et al. MiR-146a down-regulates inflammatory response by targeting TLR3 and TRAF6 in Coxsackievirus B infection. RNA 26, 91\u2013100. https:\/\/doi.org\/10.1261\/rna.071985.119 (2020).","journal-title":"RNA"},{"key":"38367_CR15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1182\/blood.2019002045","volume":"135","author":"YL Su","year":"2020","unstructured":"Su, Y. L. et al. Myeloid cell-targeted miR-146a mimic inhibits NF-\u03baB-driven inflammation and leukemia progression in vivo. Blood 135, 167\u2013180. https:\/\/doi.org\/10.1182\/blood.2019002045 (2020).","journal-title":"Blood"},{"key":"38367_CR16","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1476-4598-12-86","volume":"12","author":"B Hoesel","year":"2013","unstructured":"Hoesel, B. & Schmid, J. A. The complexity of NF-\u03baB signaling in inflammation and cancer. Mol. Cancer 12, 86. https:\/\/doi.org\/10.1186\/1476-4598-12-86 (2013).","journal-title":"Mol. Cancer"},{"key":"38367_CR17","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3389\/fnins.2020.00311","volume":"14","author":"GJ Liu","year":"2020","unstructured":"Liu, G. J. et al. MiR-146a ameliorates hemoglobin-induced microglial inflammatory response via TLR4\/IRAK1\/TRAF6 associated pathways. Front. Neurosci. 14, 311. https:\/\/doi.org\/10.3389\/fnins.2020.00311 (2020).","journal-title":"Front. Neurosci."},{"key":"38367_CR18","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.intimp.2018.12.043","volume":"68","author":"H Wu","year":"2019","unstructured":"Wu, H. et al. Extracellular vesicles containing miR-146a attenuate experimental colitis by targeting TRAF6 and IRAK1. Int. Immunopharmacol. 68, 204\u2013212. https:\/\/doi.org\/10.1016\/j.intimp.2018.12.043 (2019).","journal-title":"Int. Immunopharmacol."},{"key":"38367_CR19","doi-asserted-by":"publisher","first-page":"197671","DOI":"10.1016\/j.virusres.2019.197671","volume":"271","author":"X Zhang","year":"2019","unstructured":"Zhang, X. et al. miR-146a promotes Borna disease virus 1 replication through IRAK1\/TRAF6\/NF-\u03baB signaling pathway. Virus Res. 271, 197671. https:\/\/doi.org\/10.1016\/j.virusres.2019.197671 (2019).","journal-title":"Virus Res."},{"key":"38367_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1172\/jci11837","volume":"107","author":"G Zhang","year":"2001","unstructured":"Zhang, G. & Ghosh, S. Toll-like receptor-mediated NF-kappaB activation: A phylogenetically conserved paradigm in innate immunity. J. Clin. Investig. 107, 13\u201319. https:\/\/doi.org\/10.1172\/jci11837 (2001).","journal-title":"J. Clin. Investig."},{"key":"38367_CR21","doi-asserted-by":"publisher","first-page":"110993","DOI":"10.1016\/j.biopha.2020.110993","volume":"133","author":"L He","year":"2021","unstructured":"He, L. et al. Dexmedetomidine exerts cardioprotective effect through miR-146a-3p targeting IRAK1 and TRAF6 via inhibition of the NF-\u03baB pathway. Biomed. Pharmacother. 133, 110993. https:\/\/doi.org\/10.1016\/j.biopha.2020.110993 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"38367_CR22","doi-asserted-by":"publisher","first-page":"5307","DOI":"10.1038\/s41388-020-1363-8","volume":"39","author":"DF Meng","year":"2020","unstructured":"Meng, D. F. et al. S100A14 suppresses metastasis of nasopharyngeal carcinoma by inhibition of NF-kB signaling through degradation of IRAK1. Oncogene 39, 5307\u20135322. https:\/\/doi.org\/10.1038\/s41388-020-1363-8 (2020).","journal-title":"Oncogene"},{"key":"38367_CR23","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1080\/15548627.2018.1474995","volume":"14","author":"Y Min","year":"2018","unstructured":"Min, Y., Kim, M. J., Lee, S., Chun, E. & Lee, K. Y. Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation. Autophagy 14, 1347\u20131358. https:\/\/doi.org\/10.1080\/15548627.2018.1474995 (2018).","journal-title":"Autophagy"},{"key":"38367_CR24","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jep.2017.12.041","volume":"215","author":"SW Kang","year":"2018","unstructured":"Kang, S. W. et al. A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model. J. Ethnopharmacol. 215, 91\u2013100. https:\/\/doi.org\/10.1016\/j.jep.2017.12.041 (2018).","journal-title":"J. Ethnopharmacol."},{"key":"38367_CR25","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.1167\/iovs.13-13577","volume":"55","author":"Z Zhang","year":"2014","unstructured":"Zhang, Z. et al. Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model. Investig. Ophthalmol. Vis. Sci. 55, 2963\u20132974. https:\/\/doi.org\/10.1167\/iovs.13-13577 (2014).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"38367_CR26","doi-asserted-by":"publisher","first-page":"9230","DOI":"10.26355\/eurrev_201911_19415","volume":"23","author":"X Chen","year":"2019","unstructured":"Chen, X. et al. MiR-146a alleviates inflammation of acute gouty arthritis rats through TLR4\/MyD88 signal transduction pathway. Eur. Rev. Med. Pharmacol. Sci. 23, 9230\u20139237. https:\/\/doi.org\/10.26355\/eurrev_201911_19415 (2019).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"38367_CR27","doi-asserted-by":"publisher","first-page":"L727","DOI":"10.1152\/ajplung.00174.2014","volume":"307","author":"BS Comer","year":"2014","unstructured":"Comer, B. S. et al. MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 307, L727\u2013L734. https:\/\/doi.org\/10.1152\/ajplung.00174.2014 (2014).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"38367_CR28","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.2174\/138161206778343028","volume":"12","author":"CC Chen","year":"2006","unstructured":"Chen, C. C. Signal transduction pathways of inflammatory gene expressions and therapeutic implications. Curr. Pharm. Des. 12, 3497\u20133508. https:\/\/doi.org\/10.2174\/138161206778343028 (2006).","journal-title":"Curr. Pharm. Des."},{"key":"38367_CR29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ejim.2012.10.009","volume":"24","author":"R de Pablo","year":"2013","unstructured":"de Pablo, R. et al. Circulating sICAM-1 and sE-selectin as biomarker of infection and prognosis in patients with systemic inflammatory response syndrome. Eur. J. Intern. Med. 24, 132\u2013138. https:\/\/doi.org\/10.1016\/j.ejim.2012.10.009 (2013).","journal-title":"Eur. J. Intern. Med."},{"key":"38367_CR30","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1021\/acs.jproteome.9b00149","volume":"18","author":"X Chen","year":"2019","unstructured":"Chen, X. et al. Integrated tear proteome and metabolome reveal panels of inflammatory-related molecules via key regulatory pathways in dry eye syndrome. J. Proteome Res. 18, 2321\u20132330. https:\/\/doi.org\/10.1021\/acs.jproteome.9b00149 (2019).","journal-title":"J. Proteome Res."},{"key":"38367_CR31","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/icl.0000000000000042","volume":"40","author":"Y Wei","year":"2014","unstructured":"Wei, Y. & Asbell, P. A. The core mechanism of dry eye disease is inflammation. Eye Contact Lens 40, 248\u2013256. https:\/\/doi.org\/10.1097\/icl.0000000000000042 (2014).","journal-title":"Eye Contact Lens"},{"key":"38367_CR32","first-page":"257","volume":"17","author":"Z Lin","year":"2011","unstructured":"Lin, Z. et al. A mouse dry eye model induced by topical administration of benzalkonium chloride. Mol. Vis. 17, 257\u2013264 (2011).","journal-title":"Mol. Vis."},{"key":"38367_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030509","author":"Q Yang","year":"2017","unstructured":"Yang, Q. et al. A comparison of the effects of benzalkonium chloride on ocular surfaces between C57BL\/6 and BALB\/c mice. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms18030509 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"38367_CR34","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1089\/jop.2021.0044","volume":"38","author":"CH Liao","year":"2022","unstructured":"Liao, C. H., Tseng, C. L., Lin, S. L., Liang, C. L. & Juo, S. H. MicroRNA therapy for dry eye disease. J. Ocul. Pharmacol. Ther. 38, 125\u2013132. https:\/\/doi.org\/10.1089\/jop.2021.0044 (2022).","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"38367_CR35","doi-asserted-by":"publisher","first-page":"7484","DOI":"10.1038\/s41598-020-64422-5","volume":"10","author":"Q Pilson","year":"2020","unstructured":"Pilson, Q., Smith, S., Jefferies, C. A., Gabhann-Dromgoole, J. N. & Murphy, C. C. miR-744\u20135p contributes to ocular inflammation in patients with primary Sjogrens Syndrome. Sci. Rep. 10, 7484. https:\/\/doi.org\/10.1038\/s41598-020-64422-5 (2020).","journal-title":"Sci. Rep."},{"key":"38367_CR36","doi-asserted-by":"publisher","first-page":"e23571","DOI":"10.1002\/jcla.23571","volume":"35","author":"L Yin","year":"2021","unstructured":"Yin, L., Zhang, M., He, T. & Chen, S. The expression of miRNA-146a-5p and its mechanism of treating dry eye syndrome. J. Clin. Lab. Anal. 35, e23571. https:\/\/doi.org\/10.1002\/jcla.23571 (2021).","journal-title":"J. Clin. Lab. Anal."},{"key":"38367_CR37","doi-asserted-by":"publisher","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","volume":"1","author":"T Lawrence","year":"2009","unstructured":"Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol. 1, a001651. https:\/\/doi.org\/10.1101\/cshperspect.a001651 (2009).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"38367_CR38","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","volume":"5","author":"H Yu","year":"2020","unstructured":"Yu, H., Lin, L., Zhang, Z., Zhang, H. & Hu, H. Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct. Target. Ther. 5, 209. https:\/\/doi.org\/10.1038\/s41392-020-00312-6 (2020).","journal-title":"Signal Transduct. Target. Ther."},{"key":"38367_CR39","doi-asserted-by":"publisher","first-page":"15689","DOI":"10.1074\/jbc.M801346200","volume":"283","author":"J Hartupee","year":"2008","unstructured":"Hartupee, J., Li, X. & Hamilton, T. Interleukin 1alpha-induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1. J. Biol. Chem. 283, 15689\u201315693. https:\/\/doi.org\/10.1074\/jbc.M801346200 (2008).","journal-title":"J. Biol. Chem."},{"key":"38367_CR40","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1016\/j.bcp.2013.09.017","volume":"86","author":"Q Liu","year":"2013","unstructured":"Liu, Q. et al. SC-514, a selective inhibitor of IKK\u03b2 attenuates RANKL-induced osteoclastogenesis and NF-\u03baB activation. Biochem. Pharmacol. 86, 1775\u20131783. https:\/\/doi.org\/10.1016\/j.bcp.2013.09.017 (2013).","journal-title":"Biochem. Pharmacol."},{"key":"38367_CR41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cellsig.2018.12.004","volume":"55","author":"MJ Bloom","year":"2019","unstructured":"Bloom, M. J. et al. The effects of IKK-beta inhibition on early NF-kappa-B activation and transcription of downstream genes. Cell. Signal. 55, 17\u201325. https:\/\/doi.org\/10.1016\/j.cellsig.2018.12.004 (2019).","journal-title":"Cell. Signal."},{"key":"38367_CR42","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jtos.2022.06.001","volume":"25","author":"AJ Poe","year":"2022","unstructured":"Poe, A. J. et al. Regulatory role of miR-146a in corneal epithelial wound healing via its inflammatory targets in human diabetic cornea. Ocul. Surf. 25, 92\u2013100. https:\/\/doi.org\/10.1016\/j.jtos.2022.06.001 (2022).","journal-title":"Ocul. Surf."},{"key":"38367_CR43","doi-asserted-by":"publisher","first-page":"4944","DOI":"10.1167\/iovs.13-13631","volume":"55","author":"C Cowan","year":"2014","unstructured":"Cowan, C. et al. MicroRNA-146 inhibits thrombin-induced NF-\u03baB activation and subsequent inflammatory responses in human retinal endothelial cells. Investig. Ophthalmol. Vis. Sci. 55, 4944\u20134951. https:\/\/doi.org\/10.1167\/iovs.13-13631 (2014).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"38367_CR44","doi-asserted-by":"publisher","first-page":"2976","DOI":"10.1167\/iovs.09-4874","volume":"51","author":"G Li","year":"2010","unstructured":"Li, G., Luna, C., Qiu, J., Epstein, D. L. & Gonzalez, P. Modulation of inflammatory markers by miR-146a during replicative senescence in trabecular meshwork cells. Investig. Ophthalmol. Vis. Sci. 51, 2976\u20132985. https:\/\/doi.org\/10.1167\/iovs.09-4874 (2010).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"38367_CR45","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/jlb.2mr0220-549r","volume":"108","author":"TM Bui","year":"2020","unstructured":"Bui, T. M., Wiesolek, H. L. & Sumagin, R. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J. Leukoc. Biol. 108, 787\u2013799. https:\/\/doi.org\/10.1002\/jlb.2mr0220-549r (2020).","journal-title":"J. Leukoc. Biol."},{"key":"38367_CR46","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1038\/mi.2015.135","volume":"9","author":"R Sumagin","year":"2016","unstructured":"Sumagin, R. et al. Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing. Mucosal Immunol. 9, 1151\u20131162. https:\/\/doi.org\/10.1038\/mi.2015.135 (2016).","journal-title":"Mucosal Immunol."},{"key":"38367_CR47","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/cdd.2011.140","volume":"19","author":"JY Kim","year":"2012","unstructured":"Kim, J. Y. et al. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-\u03b2 plaques. Cell Death Differ. 19, 680\u2013691. https:\/\/doi.org\/10.1038\/cdd.2011.140 (2012).","journal-title":"Cell Death Differ."},{"key":"38367_CR48","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.exer.2010.08.007","volume":"91","author":"D Gagen","year":"2010","unstructured":"Gagen, D. et al. ICAM-1 mediates surface contact between neutrophils and keratocytes following corneal epithelial abrasion in the mouse. Exp. Eye Res. 91, 676\u2013684. https:\/\/doi.org\/10.1016\/j.exer.2010.08.007 (2010).","journal-title":"Exp. Eye Res."},{"key":"38367_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102175","author":"AJ Poe","year":"2020","unstructured":"Poe, A. J. et al. Integrated transcriptome and proteome analyses reveal the regulatory role of miR-146a in human limbal epithelium via notch signaling. Cells https:\/\/doi.org\/10.3390\/cells9102175 (2020).","journal-title":"Cells"},{"key":"38367_CR50","doi-asserted-by":"publisher","first-page":"108685","DOI":"10.1016\/j.exer.2021.108685","volume":"210","author":"C Chu","year":"2021","unstructured":"Chu, C. et al. \u03b1-MSH ameliorates corneal surface dysfunction in scopolamine-induced dry eye rats and human corneal epithelial cells via enhancing EGFR expression. Exp. Eye Res. 210, 108685. https:\/\/doi.org\/10.1016\/j.exer.2021.108685 (2021).","journal-title":"Exp. Eye Res."},{"key":"38367_CR51","doi-asserted-by":"publisher","first-page":"28145","DOI":"10.1038\/srep28145","volume":"6","author":"Y Chen","year":"2016","unstructured":"Chen, Y. et al. MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea. Sci. Rep. 6, 28145. https:\/\/doi.org\/10.1038\/srep28145 (2016).","journal-title":"Sci. Rep."},{"key":"38367_CR52","doi-asserted-by":"publisher","first-page":"106468","DOI":"10.1016\/j.intimp.2020.106468","volume":"83","author":"Y Zhou","year":"2020","unstructured":"Zhou, Y. et al. Blockade of extracellular high-mobility group box 1 attenuates inflammation-mediated damage and haze grade in mice with corneal wounds. Int. Immunopharmacol. 83, 106468. https:\/\/doi.org\/10.1016\/j.intimp.2020.106468 (2020).","journal-title":"Int. Immunopharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38367-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38367-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38367-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T22:02:15Z","timestamp":1689199335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-38367-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,11]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["38367"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-38367-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,11]]},"assertion":[{"value":"5 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11192"}}