{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:48:28Z","timestamp":1791823708931,"version":"4.3.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ultraviolet B (UVB) radiation is a major environmental factor contributing to skin damage via DNA damage, oxidative stress, inflammation, and collagen degradation. It penetrates the epidermis, disrupts DNA integrity, and generates reactive oxygen species (ROS), activating pro-inflammatory pathways such as NF-\u03baB and AP-1, and inducing matrix metalloproteinases (MMPs). These processes lead to structural skin changes, inflammation, and pigmentation disorders like melasma. Cumulative DNA damage from UVB also drives photocarcinogenesis, with nearly 90% of melanomas associated with UV radiation (UVR). Despite clinical interventions like phototherapy and antioxidants, effective treatments for UVB-induced damage remain limited due to side effects and efficacy issues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study investigates the protective effects of curcumin on UVB-induced skin damage using a mouse UVB irradiation model and HaCaT cells exposed to UVB <jats:italic>in vitro<\/jats:italic>. Skin damage was assessed through histopathological and immunohistochemical analyses. Cellular functional changes were evaluated using assays for cell viability, mitochondrial function, ROS levels, and apoptosis. Transcriptomic analysis was employed to elucidate the molecular mechanisms underlying curcumin\u2019s protective effects on HaCaT cells post-UVB exposure. This integrated approach provides a comprehensive understanding of curcumin\u2019s molecular-level protection against UVB-induced skin damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Curcumin significantly alleviated UVB-induced skin lesions and inflammation <jats:italic>in vivo<\/jats:italic>. <jats:italic>In vitro<\/jats:italic>, it mitigated UVB-induced HaCaT cell damage, enhancing viability while reducing apoptosis and ROS levels. Transcriptomic analysis revealed that curcumin upregulated YAP signaling and mitochondrial autophagy while suppressing IL-18 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Curcumin treatment markedly improved UVB-induced skin lesions and reduced epidermal inflammation and thickness <jats:italic>in vivo<\/jats:italic>. <jats:italic>In vitro<\/jats:italic>, curcumin intervention alleviated UVB-induced HaCaT cell damage, including reduced viability, increased apoptosis, elevated ROS and DNA damage, and enhanced inflammatory responses. Transcriptomic analysis demonstrated that curcumin upregulated the YAP signaling pathway and mitochondrial autophagy while inhibiting the IL-18 pathway. Further studies revealed that curcumin directly interacts with YAP1, promoting mitochondrial autophagy, an effect blocked by the YAP1 inhibitor Verteporfin. Additionally, curcumin enhances mitochondrial function through YAP1, maintaining mitochondrial integrity and preventing the release of mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS), thereby suppressing NLRP3\/IL-18 pathway activation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1566287","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T07:43:49Z","timestamp":1742888629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage"],"prefix":"10.3389","volume":"16","author":[{"given":"Quan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengmei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoquan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jphotobiol.2024.112937","article-title":"Baicalin attenuates acute skin damage induced by ultraviolet B via inhibiting pyroptosis","volume":"256","author":"Liu","year":"2024","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/exd.15109","article-title":"Ultraviolet B irradiation increases the expression of cornulin and retepin in human skin xenotransplants","volume":"33","author":"Makino","year":"2024","journal-title":"Exp Dermatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/jpi.2018.65.issue-2","article-title":"Melatonin and its derivatives counteract the ultraviolet B radiation-induced damage in human and porcine skin ex vivo","volume":"65","author":"Skobowiat","year":"2018","journal-title":"J Pineal Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.12.008","article-title":"Naringin protects ultraviolet B-induced skin damage by regulating p38 MAPK signal pathway","volume":"82","author":"Ren","year":"2016","journal-title":"J Dermatol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2016.04.027","article-title":"7-Hydroxycoumarin prevents UVB-induced activation of NF-\u03baB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells","volume":"161","author":"Karthikeyan","year":"2016","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jphotobiol.2022.112568","article-title":"Ultraviolet B irradiation induces senescence of human corneal endothelial cells in vitro by DNA damage response and oxidative stress","volume":"235","author":"Jiang","year":"2022","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/jfbc.2019.43.issue-2","article-title":"Protective effects of hawthorn (Crataegus pinnatifida) polyphenol extract against UVB-induced skin damage by modulating the p53 mitochondrial pathway in vitro and in vivo","volume":"43","author":"Liu","year":"2019","journal-title":"J Food Biochem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2016.022","article-title":"Baicalein protects human skin cells against ultraviolet B-induced oxidative stress","volume":"24","author":"Oh","year":"2016","journal-title":"Biomol Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/jbt.22263","article-title":"Naringin prevents ultraviolet-B radiation-induced oxidative damage and inflammation through activation of peroxisome proliferator-activated receptor \u03b3 in mouse embryonic fibroblast (NIH-3T3) cells","volume":"33","author":"Das","year":"2019","journal-title":"J Biochem Mol Toxicol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/antiox13040406","article-title":"Sulforaphane inhibits IL-1\u03b2-induced IL-6 by suppressing ROS production, AP-1, and STAT3 in colorectal cancer HT-29 cells","volume":"13","author":"Sah","year":"2024","journal-title":"Antioxidants"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.12.002","article-title":"TNF and ROS crosstal in inflammation","volume":"26","author":"Blaser","year":"2016","journal-title":"Trends Cell Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2340\/00015555-3758","article-title":"Risk of skin cancer among patients with chronic kidney disease treated with ultraviolet B phototherapy for uraemic pruritus: A nationwide cohort study","volume":"101","author":"Ko","year":"2021","journal-title":"Acta Dermato-Venereologica"},{"key":"B13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12889-021-11089-w","article-title":"Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer","volume":"21","author":"Purushothaman","year":"2021","journal-title":"BMC Public Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.redox.2021.101924","article-title":"Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis","volume":"41","author":"Addison","year":"2021","journal-title":"Redox Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.2016.21.issue-2","article-title":"High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) pathway protects melanocytes and melanoma from UVB-induced apoptosis","volume":"21","author":"Fukumoto","year":"2016","journal-title":"Genes to Cells"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/1047-2797(93)90017-X","article-title":"Rising trends in melanoma. An hypothesis concerning sunscreen effectiveness","volume":"3","author":"Garland","year":"1993","journal-title":"Ann Epidemiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.02.012","article-title":"Photo-protective effect of sargachromenol against UVB radiation-induced damage through modulating cellular antioxidant systems and apoptosis in human keratinocytes","volume":"43","author":"Fernando","year":"2016","journal-title":"Environ Toxicol Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.2017.21.issue-2","article-title":"Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK\/AP-1 and activation of Nrf2-ARE antioxidant system","volume":"21","author":"Sun","year":"2017","journal-title":"J Cell Mol Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2015.131","article-title":"Mitochondria-targeted vitamin E protects skin from UVB-irradiation","volume":"24","author":"Kim","year":"2016","journal-title":"Biomol Ther"},{"key":"B20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/ijms17071026","article-title":"Fernblock (Polypodium leucotomos extract): molecular mechanisms and pleiotropic effects in light-related skin conditions, photoaging and skin cancers, a review","volume":"17","author":"Parrado","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2016.10.011","article-title":"Preventive effect of Rhus javanica extract on UVB-induced skin inflammation and photoaging","volume":"27","author":"Ha","year":"2016","journal-title":"J Funct Foods"},{"key":"B22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.heliyon.2023.e21955","article-title":"The extract from Portulaca oleracea L. rehabilitates skin photoaging via adjusting miR-138-5p\/Sirt1-mediated inflammation and oxidative stress","volume":"9","author":"Qu","year":"2023","journal-title":"Heliyon"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01598-8","article-title":"Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin","volume":"71","author":"Salminen","year":"2022","journal-title":"Inflammation Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/bab.v69.3","article-title":"Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin","volume":"69","author":"Chen","year":"2022","journal-title":"Biotechnol Appl Biochem"},{"key":"B25","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jphotobiol.2021.112304","article-title":"Anti-damage effect of theaflavin-3\u2032-gallate from black tea on UVB-irradiated HaCaT cells by photoprotection and maintaining cell homeostasis","volume":"224","author":"Zheng","year":"2021","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14174","article-title":"Astragaloside prevents UV-induced keratinocyte injury by regulating TLR4\/NF-\u03baB pathway","volume":"21","author":"Wang","year":"2022","journal-title":"J Cosmetic Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1134\/S2079057020020046","article-title":"Experimental and clinical studies of mechanisms of the antiaging effects of chemical compounds in Astragalus membranaceus (Review)","volume":"10","author":"Berezutsky","year":"2020","journal-title":"Adv Gerontol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/cosmetics10030083","article-title":"Food Supplements for Skin Health: In Vitro Efficacy of a Combination of Rhodiola rosea, Tribulus terrestris, Moringa oleifera and Undaria pinnatifida on UV-Induced Damage","volume":"10","author":"Paganelli","year":"2023","journal-title":"Cosmetics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.v20.12","article-title":"Efficacy and safety of Resveratrol combined with Ablative Fractional CO2 laser system in the treatment of skin photoaging","volume":"20","author":"Du","year":"2021","journal-title":"J Cosmetic Dermatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-024-10099-6","article-title":"Resveratrol activates autophagy and protects from UVA-induced photoaging in human skin fibroblasts and the skin of male mice by regulating the AMPK pathway","volume":"25","author":"Xia","year":"2024","journal-title":"Biogerontology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/jfbc.12598","article-title":"Preventive effect of Curcuma zedoaria extract on UVB-induced skin inflammation and photoaging","volume":"42","author":"Ha","year":"2018","journal-title":"J Food Biochem"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1042\/BSR20180849","article-title":"Effects of FM0807, a novel curcumin derivative, on lipopolysaccharide-induced inflammatory factor release via the ROS\/JNK\/p53 pathway in RAW264.7 cells","volume":"38","author":"Wu","year":"2018","journal-title":"Biosci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9749","article-title":"Curcumin inhibits high glucose-induced inflammatory injury in human retinal pigment epithelial cells through the ROS-PI3K\/AKT\/mTOR signaling pathway","volume":"19","author":"Ran","year":"2019","journal-title":"Mol Med Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-018-0466-0","article-title":"Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by regulating JNK\/NF-kB pathway and ROS production","volume":"26","author":"Sadeghi","year":"2018","journal-title":"Inflammopharmacology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/adhm.202303016","article-title":"Dual-ROS sensitive moieties conjugate inhibits curcumin oxidative degradation for colitis precise therapy","volume":"13","author":"Liang","year":"2024","journal-title":"Advanced Healthc Mater"},{"key":"B36","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12951-023-01976-2","article-title":"Dual sensitive supramolecular curcumin nanoparticles\u201d in \u201cadvanced yeast particles\u201d mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment","volume":"21","author":"Han","year":"2023","journal-title":"J Nanobiotechnol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jphotobiol.2014.09.004","article-title":"Antioxidants in the prevention of UVB-induced keratynocyte apoptosis","volume":"141","author":"Salucci","year":"2014","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.intimp.2023.111357","article-title":"Doxercalciferol alleviates UVB-induced HaCaT cell senescence and skin photoaging","volume":"127","author":"Ge","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"9993","DOI":"10.1080\/21655979.2021.1994720","article-title":"Curcumin protection against ultraviolet-induced photo-damage in Hacat cells by regulating nuclear factor erythroid 2-related factor 2","volume":"12","author":"Deng","year":"2021","journal-title":"Bioengineered"},{"key":"B40","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/molecules28010371","article-title":"Single or daily application of topical curcumin prevents ultraviolet B-induced apoptosis in mice","volume":"28","author":"Djawad","year":"2023","journal-title":"Molecules"},{"key":"B41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jphotobiol.2019.111771","article-title":"Abilities of protocatechuic acid and its alkyl esters, ethyl and heptyl protocatechuates, to counteract UVB-induced oxidative injuries and photoaging in fibroblasts L929 cell line","volume":"203","author":"Dar\u00e9","year":"2020","journal-title":"J Photochem Photobiol B-Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/antiox9030255","article-title":"Rosemary diterpenes and flavanone aglycones provide improved genoprotection against UV-induced DNA damage in a human skin cell model","volume":"9","author":"S\u00e1nchez-Marzo","year":"2020","journal-title":"Antioxidants"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1566287\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T07:43:53Z","timestamp":1742888633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1566287\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2025.1566287"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1566287","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]},"article-number":"1566287"}}