{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:57:35Z","timestamp":1787885855086,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alopecia is a highly prevalent hair loss disorder characterized by an abnormality in hair cycling. Induction of autophagy and secretion of growth factors by adipocyte precursors are sufficient to activate quiescent hair follicles, yet therapies targeting these processes remain limited. Here, we identify rebamipide\u2014a drug originally intended for gastric ulcer treatment\u2014as a promising candidate for hair regeneration by modulating dermal adipocyte metabolism. Topical rebamipide treatment induces autophagy and adipose triglyceride lipase (ATGL)-mediated lipolysis in dermal adipocytes. Using primary culture systems, we demonstrate that rebamipide-driven lipolysis triggers adipocyte dedifferentiation, activating hair follicle stem cells (HFSCs) via elevated platelet-derived growth factor (PDGF) levels. Mechanistically, computer simulations and target validation experiments confirm that rebamipide directly binds to the prostaglandin E receptor EP4, triggering PI3K\/ERK-dependent autophagy and lipolysis. Collectively, our findings highlight EP4 as a novel therapeutic target for hair loss and position rebamipide as an agent that couples lipid metabolism remodeling with HFSC activation.<\/jats:p>","DOI":"10.3390\/ijms262010132","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:18:54Z","timestamp":1760948334000},"page":"10132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rebamipide Induces Hair Regeneration Through EP4-Driven Lipid Metabolism Remodeling"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5682","authenticated-orcid":false,"given":"Chenjie","family":"Feng","sequence":"first","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-6818","authenticated-orcid":false,"given":"Hao","family":"Dong","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-1502","authenticated-orcid":false,"given":"Dongyue","family":"Jiang","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-7410","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9516-1466","authenticated-orcid":false,"given":"Xinyue","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-3322","authenticated-orcid":false,"given":"Weiwei","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2933-8715","authenticated-orcid":false,"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9398-3308","authenticated-orcid":false,"given":"Dayang","family":"Xu","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7774-1577","authenticated-orcid":false,"given":"Ruixin","family":"Li","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-3964","authenticated-orcid":false,"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/j.1749-6632.1951.tb31971.x","article-title":"Patterned loss of hair in man; types and incidence","volume":"53","author":"Hamilton","year":"1951","journal-title":"Ann. 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