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In this study, we identified a peptide (DL-13) from Periplaneta americana L. and explored its role and mechanisms in skin wound healing. In vitro, the effects of DL-13 on proliferation, migration, and related gene\/protein expression in HaCaT keratinocytes were assessed via qRT-PCR and Western blot. In vivo, rat wound healing assays confirmed its efficacy. Results showed DL-13 accelerated rat wound healing. In in vitro studies, DL-13 activated EGFR and its downstream PI3K\/AKT\/mTOR, ERK\/MAPK, and JAK2\/STAT3 pathways, upregulated EMT-related proteins (N-cadherin, MMP-2, p-FAK, \u03b2-catenin), partially regulated macrophage cytokine secretion, and promoted HaCaT proliferation\/migration, thereby facilitating re-epithelialization at skin injury sites. Overall, DL-13 may enhance the function of HaCaT cells by activating the EGFR signaling pathway and regulate inflammatory factors in macrophages, thereby promoting the healing of skin wounds in rats. The results of this study will lay an experimental and scientific foundation for the discovery of new compounds for wound healing and their application.<\/jats:p>","DOI":"10.3390\/molecules31081355","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:57:21Z","timestamp":1776758241000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effects and Molecular Mechanisms of a Peptide from Periplaneta americana L. in Skin Wound Healing"],"prefix":"10.3390","volume":"31","author":[{"given":"Honghong","family":"Qiu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjin","family":"Tang","sequence":"additional","affiliation":[{"name":"Hybio Pharmaceutical Co., Ltd., Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-7463","authenticated-orcid":false,"given":"Zhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Key Laboratory of Innovative Technologies for Natural Product Cosmetics Raw Materials, Guangdong Provincial Medical Products Administration, Guangzhou 510632, China"},{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.276.5309.75","article-title":"Wound healing\u2014Aiming for perfect skin regeneration","volume":"276","author":"Martin","year":"1997","journal-title":"Science"},{"key":"ref_2","unstructured":"Montagna, W. 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