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However, the mechanism by which proinflammatory cytokines modulate corneal epithelial wound healing remains unclear. In this study, we found that IL\u20101\u03b2 or TNF\u2010\u03b1 was transiently elevated during corneal epithelial wound healing in mice. After corneal epithelial debridement, persistent treatment with IL\u20101\u03b2 or TNF\u2010\u03b1 restrained the level of phosphorylated signal transducer and activator of transcription 3 (p\u2010STAT3) and boosted the level of cell cycle inhibitor p16<jats:sup>Ink4a<\/jats:sup>, resulting in impaired corneal epithelial repair. When <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>Ink4a<\/jats:italic><\/jats:sup> was deleted, the p\u2010STAT3 level in corneal epithelium was enhanced and corneal epithelial wound healing was clearly accelerated. In diabetic mice, IL\u20101\u03b2, TNF\u2010\u03b1, and p16<jats:sup>Ink4a<\/jats:sup> appeared a sustained and strong expression in the corneal epithelium, and <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>Ink4a<\/jats:italic><\/jats:sup> knockdown partially reverted the defective diabetic corneal epithelial repair. Furthermore, immunoprecipitation proved that p16<jats:sup>Ink4a<\/jats:sup> interacted with p\u2010STAT3 and thus possibly suppressed the STAT3 activity. Our findings revealed a novel mechanism that the proinflammatory cytokines modulate corneal epithelial wound healing via the p16<jats:sup>Ink4a<\/jats:sup>\u2010STAT3 signaling.<\/jats:p>","DOI":"10.1002\/jcp.29823","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T15:15:10Z","timestamp":1590938110000},"page":"10081-10093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["The proinflammatory cytokines IL\u20101\u03b2 and TNF\u2010\u03b1 modulate corneal epithelial wound healing through p16<sup>Ink4a<\/sup> suppressing STAT3 activity"],"prefix":"10.1002","volume":"235","author":[{"given":"Xiaolei","family":"Wang","sequence":"first","affiliation":[{"name":"Medical College, Qingdao University  Qingdao China"},{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muchen","family":"Dong","sequence":"additional","affiliation":[{"name":"Shandong Eye Hospital, Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan Mingshui Eye Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-8042","authenticated-orcid":false,"given":"Lingling","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.038"},{"issue":"1","key":"e_1_2_9_3_1","first-page":"5","article-title":"Corneal epithelial wound healing","volume":"51","author":"Agrawal V. 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