{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:33:26Z","timestamp":1785407606147,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LIBON Inc.","award":["LIBON-2506-01"],"award-info":[{"award-number":["LIBON-2506-01"]}]},{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"crossref","award":["GCU-202403920001"],"award-info":[{"award-number":["GCU-202403920001"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"crossref"}]},{"award":["GCU-202403920001"],"award-info":[{"award-number":["GCU-202403920001"]}],"id":[{"id":"https:\/\/ror.org\/03ryywt80","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Platelet-rich plasma (PRP) is widely utilized for skin rejuvenation and tissue regeneration; however, its biological effects vary according to leukocyte content and molecular composition. We investigated the mechanism by which leukocyte-rich PRP (L-PRP) enhances extracellular matrix (ECM) regeneration in aged skin, focusing on the CCL1-CCR8\/pyruvate kinase M2 (PKM2) signaling axis. First, we demonstrated that L-PRP contains significantly higher levels of CCL1 than platelet-poor plasma (PPP). In senescent human dermal fibroblasts, L-PRP increased CCL1-CCR8 interactions in a manner linked to enhanced formation and nuclear translocation of PKM2 dimers. This enhancement was accompanied by Janus kinase (JAK)\/signal transducer and activator of transcription 3 (STAT3) pathway activation and the upregulation of STAT3-dependent anti-apoptotic proteins (Bcl-2, Bcl-xL) and proliferative markers (Cyclin D1), resulting in increased fibroblast proliferation. Furthermore, L-PRP increased PKM2 tetramer levels, promoted PKM2-SMAD7 binding, and reduced SMAD7-mediated inhibition of transforming growth factor (TGF)-\u03b2 signaling, leading to enhanced SMAD2\/3 activation. These molecular events augmented the synthesis of collagen types I and III in senescent fibroblasts. In aged mice, intradermal L-PRP injections elicited dose-dependent increases in fibroblast proliferation, collagen fiber deposition, and skin elasticity. Nuclear PKM2 dimer\/STAT3 signaling and PKM2 tetramer\/TGF-\u03b2 signaling were both more strongly activated in the L-PRP group. Our findings identify PKM2 as a central metabolic and signaling integrator linking immune-derived chemokines to fibroblast rejuvenation. This study provides mechanistic insights concerning how L-PRP promotes ECM regeneration in aged skin via coordinated regulation of fibroblast survival, proliferation, and collagen synthesis.<\/jats:p>","DOI":"10.3390\/ijms27146281","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:29:39Z","timestamp":1784100579000},"page":"6281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leukocyte-Rich Platelet-Rich Plasma (L-PRP) Promotes Rejuvenation of Senescent Fibroblasts and Dermal Remodeling via CCL1-CCR8 Signaling and PKM2 Modulation"],"prefix":"10.3390","volume":"27","author":[{"given":"Seyeon","family":"Oh","sequence":"first","affiliation":[{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"LIBON Inc., Incheon 22006, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-5813","authenticated-orcid":false,"given":"Hyoung Moon","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Maylin Apgujeong Clinic, Seoul 06024, Republic of Korea"},{"name":"Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wook","family":"Oh","sequence":"additional","affiliation":[{"name":"Maylin Clinic the Hyundai, Seoul 07335, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4671-1135","authenticated-orcid":false,"given":"Gwahn Woo","family":"Cheon","sequence":"additional","affiliation":[{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"},{"name":"Maylin Clinic, Ilsan, Goyang 10391, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"},{"name":"Regain Clinic, Incheon 22002, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-5645","authenticated-orcid":false,"given":"Kuk Hui","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-8932","authenticated-orcid":false,"given":"Kyunghee","family":"Byun","sequence":"additional","affiliation":[{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"},{"name":"Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1468-2494.2007.00415.x","article-title":"Intrinsic and extrinsic factors in skin ageing: A review","volume":"30","author":"Farage","year":"2008","journal-title":"Int. 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