{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:53:20Z","timestamp":1790610800910,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1201205"],"award-info":[{"award-number":["2021YFF1201205"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273557 81703149 81874251 82173448"],"award-info":[{"award-number":["82273557 81703149 81874251 82173448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. <jats:italic>In vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments were conducted to verify its therapeutic role. Drug\u2013target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the <jats:italic>in vivo<\/jats:italic> experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Finally, drug\u2013target prediction and molecular docking revealed that AKT1\/MAPK1\/MMP9 could be the pharmacological targets of EGCG in rosacea.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation <jats:italic>via<\/jats:italic> inducing autophagy in keratinocytes.<\/jats:p>","DOI":"10.3389\/fphar.2023.1092473","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T04:48:37Z","timestamp":1677646117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["EGCG identified as an autophagy inducer for rosacea therapy"],"prefix":"10.3389","volume":"14","author":[{"given":"Lei","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.jid.2019.08.434","article-title":"Superoxide dismutase 3 inhibits LL-37\/KLK-5-mediated skin inflammation through modulation of EGFR and associated inflammatory cascades","volume":"140","author":"Agrahari","year":"2020","journal-title":"J. investigative dermatology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.det.2017.11.001","article-title":"Rosacea pathogenesis","volume":"36","author":"Ahn","year":"2018","journal-title":"Dermatol. 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