{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:29:17Z","timestamp":1790994557946,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504251"],"award-info":[{"award-number":["82504251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274312"],"award-info":[{"award-number":["82274312"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007547","name":"Fourth Military Medical University","doi-asserted-by":"publisher","award":["New Flyer Talent Program\u2010Eagle Plan"],"award-info":[{"award-number":["New Flyer Talent Program\u2010Eagle Plan"]}],"id":[{"id":"10.13039\/501100007547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hypertrophic scar (HS) is a cutaneous fibrotic disorder characterized by persistent myofibroblast activation and excessive extracellular matrix deposition. Elucidating the origin and characteristics of myofibroblasts remains a central focus in the field. This study identifies a novel subtype of scar myofibroblasts originating from macrophage\u2010myofibroblast transition (MMT). MMT cells constitute a significant proportion of HS myofibroblasts and drive HS progression. Multi\u2010omics analysis uncovered nicotinamide N\u2010methyltransferase (NNMT) as a metabolic orchestrator of MMT. Liquid chromatograph mass spectrometer reveals NNMT\u2010mediated depletion of nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) and\n                    <jats:italic>S<\/jats:italic>\n                    \u2010adenosyl methionine(SAM), triggering H3K27ac accumulation and H3K27me3 loss. This epigenetic reprogramming facilitated the expression of master transcription factor paired\u2010related homeobox 1 (Prrx1)\u00a0and its nuclear co\u2010condensation with super\u2010enhancer (SE) \u00a0components. Inhibition of NNMT disrupted Prrx1\u2010SE interactions, suppressed MMT in vitro, and reduced scar volume in vivo. This study 1) identifies a new origin of scar\u2010associated myofibroblasts, 2) establishes metabolite\u2010guided epigenetic alteration as a regulator of myofibroblasts cellular plasticity, and 3) nominates NNMT as a therapeutic target for HS and related fibrotic disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202502727","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:50:59Z","timestamp":1762771859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NNMT Orchestrates Metabolic\u2010Epigenetic Reprogramming to Drive Macrophage\u2010Myofibroblast Transition in Hypertrophic Scarring"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-6075","authenticated-orcid":false,"given":"Xiwen","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 710032 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 710032 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingrong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of High Talent The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi 710061 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine Beijing 100142 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 710032 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-9225","authenticated-orcid":false,"given":"Hong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Dermatology Air Force Medical Center Beijing 100039 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00474-x"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkab012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31406-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr2107204"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917663117"},{"key":"e_1_2_8_6_1","first-page":"548","volume":"29","author":"Vierhout M.","year":"2021","journal-title":"Eur. Tissue Repair Soc."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202101235"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202203076"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00716-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0270-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3629"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04713-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1204"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.104972"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30484-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.035"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041231"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.09.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202302203"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150915"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06725-x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46357-x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2218-5"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115497"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201615"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112384"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1173-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.013"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3958"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12970"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108356"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016050573"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.07.026"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004630-200021030-00005"},{"key":"e_1_2_8_35_1","first-page":"261","volume":"17","author":"Xiwen D.","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144489"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae410"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx337"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.06.010"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24110-y"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101564"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202502727","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202502727","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202502727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:28:24Z","timestamp":1772958504000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202502727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/advs.202502727"],"URL":"https:\/\/doi.org\/10.1002\/advs.202502727","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"2025-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02727"}}