{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:12Z","timestamp":1792789512668,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["RS-202300243252"],"award-info":[{"award-number":["RS-202300243252"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"award":["RS-202300243252"],"award-info":[{"award-number":["RS-202300243252"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Post-burn hypertrophic scar (HTS) formation is influenced by the dynamic balance between keratinocyte proliferation and differentiation, a process critical for maintaining skin homeostasis. Serine\/threonine kinase 33 (STK33) has emerged as a potential therapeutic target in oncology. However, its role in HTS formation remains unclear, and its effects on keratinocytes are poorly understood. We isolated human HTS-derived keratinocytes (HTSKs) from post-burn HTS tissues and treated them with ML281, originally developed as an STK33 inhibitor. We examined markers associated with keratinocyte phenotypes and functions, including proliferation (proliferating cell nuclear antigen, c-Myc, keratins 5, 14, 6, 16, and 17), epithelial\u2013mesenchymal transition (EMT; snail1, slug, twist1, e-cadherin, n-cadherin, and vimentin), differentiation (keratins 1 and 10, involucrin, loricrin, Notch1, p21, and p27), and apoptosis (cytochrome c, cleaved caspase3, Bid, Bad, Bax, and Bcl-2). mRNA and protein expression levels were assessed using reverse transcription\u2013quantitative PCR, Western blotting, and immunocytochemistry. In HTSKs, ML281 increased STK33 enzymatic activity and STK33 mRNA and protein expression, rather than inhibiting STK33 activity. ML281 treatment reduced the expression of proliferation-associated markers, promoted an EMT-associated phenotype, modulated the expression of differentiation-associated markers, and induced apoptosis-associated changes. Collectively, these findings suggest that ML281 alters post-burn HTSK phenotypes associated with proliferation, EMT, differentiation, and apoptosis.<\/jats:p>","DOI":"10.3390\/ijms27188273","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"8273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ML281 Does Not Function as an STK33 Inhibitor but Modulates Proliferation and Differentiation of Keratinocytes Derived from Hypertrophic Scars"],"prefix":"10.3390","volume":"27","author":[{"given":"Ya Xin","family":"Zheng","sequence":"first","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Hui Song","family":"Cui","sequence":"additional","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"You Ra","family":"Lee","sequence":"additional","affiliation":[{"name":"Burn Institute, Department of Rehabilitation Medicine, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"So Young","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-3285","authenticated-orcid":false,"given":"Yoon Soo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, National Fire Hospital, Chungbuk Innovation City 27740, Republic of Korea"},{"name":"Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"In Suk","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-6382","authenticated-orcid":false,"given":"Cheong Hoon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, College of Medicine, Hangang Sacred Heart Hospital, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1600-0625.2010.01105.x","article-title":"The biology of burn injury","volume":"19","author":"Evers","year":"2010","journal-title":"Exp. 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