{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:44:57Z","timestamp":1790999097998,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072177"],"award-info":[{"award-number":["82072177"]}],"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":["82302805"],"award-info":[{"award-number":["82302805"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M722132"],"award-info":[{"award-number":["2022M722132"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M752023"],"award-info":[{"award-number":["2024M752023"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Elevated extracellular matrix (ECM) accumulation is a major contributing factor to the pathogenesis of fibrotic diseases. Recent studies have indicated that N6\u2010methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) RNA modification plays a pivotal role in modulating RNA stability and contribute to the initiation of various pathological conditions. Howbeit, the precise mechanism by which m\n                      <jats:sup>6<\/jats:sup>\n                      A influences ECM deposition remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we used hypertrophic scars (HTSs) as a paradigm to investigate ECM\u2010related diseases. We focused on the role of ALKBH5\u2010mediated m\n                      <jats:sup>6<\/jats:sup>\n                      A demethylation within the pathological progression of HTSs and examined its correlation with clinical stages. The effects of ALKBH5 ablation on ECM components were studied both in vivo and in vitro. Downstream targets of ALKBH5, along with their underlying mechanisms, were identified using integrated high\u2010throughput analysis, RNA\u2010binding protein immunoprecipitation and RNA pull\u2010down assays. Furthermore, the therapeutic potential of exogenous ALKBH5 overexpression was evaluated in fibrotic scar models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ALKBH5 was decreased in fibroblasts derived from HTS lesions and was negatively correlated with their clinical stages. Importantly, ablation of ALKBH5 promoted the expression of COL3A1, COL1A1, and ELN, leading to pathological deposition and reconstruction of the ECM both in vivo and in vitro. From a therapeutic perspective, the exogenous overexpression of ALKBH5 significantly inhibited abnormal collagen deposition in fibrotic scar models. As determined by integrated high\u2010throughput analysis, key ECM components including COL3A1, COL1A1, and ELN are direct downstream targets of ALKBH5. By means of its mechanism, ALKBH5 inhibits the expression of COL3A1, COL1A1, and ELN by removing m\n                      <jats:sup>6<\/jats:sup>\n                      A from mRNAs, thereby decreasing their stability in a YTHDF1\u2010dependent manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identified ALKBH5 as an endogenous suppressor of pathological ECM deposition, contributing to the development of a reprogrammed m6A\u2010targeted therapy for HTSs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70016","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T23:56:50Z","timestamp":1725494210000},"source":"Crossref","is-referenced-by-count":14,"title":["ALKBH5\u2010mediated m\n                    <sup>6<\/sup>\n                    A demethylation ameliorates extracellular matrix deposition in cutaneous pathological fibrosis"],"prefix":"10.1002","volume":"14","author":[{"given":"Ruoqing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenying","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-9668","authenticated-orcid":false,"given":"Tao","family":"Zan","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai P.R. 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