{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:31:00Z","timestamp":1787923860852,"version":"build-2784847793"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bordeaux Metabolome Facility"},{"name":"MetaboHUB","award":["ANR- 11-INBS-0010"],"award-info":[{"award-number":["ANR- 11-INBS-0010"]}]},{"award":["ANR- 11-INBS-0010"],"award-info":[{"award-number":["ANR- 11-INBS-0010"]}],"id":[{"id":"https:\/\/ror.org\/039gscz82","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Naolys"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hibiscus plant cell cultures were developed to produce a cosmetic ingredient with anti-ageing properties. UHPLC-DAD-MS analysis of Hibiscus plant cell cultures revealed a high content of polyphenols, particularly hydroxycinnamic acid derivatives, including caffeoyl and p-coumaroyl conjugates. The biological activity of a 50\/50 mixture of extracts from Hibiscus syriacus and Hibiscus rosa-sinensis cells was investigated in a human keratinocyte\/fibroblast co-culture model, which better reproduces the reciprocal epithelial\u2013mesenchymal interactions between epidermal keratinocytes and dermal fibroblasts than monocultures, using quantitative data-independent acquisition (DIA) LC-MS\/MS proteomics combined with functional enrichment and protein\u2013protein interaction analyses. A total of 7062 proteins were identified, of which 280 were differentially expressed (107 upregulated and 171 downregulated) following hibiscus treatment. The proteomic profile suggested coordinated molecular reprogramming associated with extracellular matrix remodelling, tissue repair, hydration, and attenuation of inflammatory signalling. Functional enrichment analysis revealed coordinated modulation of extracellular matrix organization, glycosaminoglycan metabolism, lysosomal function, cell communication, and inflammatory signalling. Upregulation of extracellular matrix and adhesion proteins, including lumican, collagen VIII, fibulin-5, syndecans, and glypicans, suggested coordinated extracellular matrix remodelling that may promote skin firmness and elasticity, while the downregulation of inflammatory regulators, including CARD16 and S100 family proteins, suggested attenuation of innate inflammatory responses. Overall, these findings provide mechanistic insights into the biological activity of Hibiscus cell culture extracts and support their potential as cosmetic ingredients promoting skin homeostasis and healthy skin ageing.<\/jats:p>","DOI":"10.3390\/biom16091243","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hibiscus Suspension Culture Extract Modulates Skin Metabolism and Cellular Pathways in Human Keratinocyte\/Fibroblast Co-Cultures: A Proteomic Approach"],"prefix":"10.3390","volume":"16","author":[{"given":"Rachid","family":"Anane","sequence":"first","affiliation":[{"name":"Naolys, 86 Route d\u2019Arcachon, 33610 Cestas-Pierroton, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Melser","sequence":"additional","affiliation":[{"name":"Elysia Bioscience, 40 Avenue Ferdinand de Lesseps, 33610 Can\u00e9jan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Renouf","sequence":"additional","affiliation":[{"name":"Polyphenols Biotech, Equipe Mol\u00e9cules d\u2019Int\u00e9r\u00eat Biologique, UMR 1366 INRAE, Facult\u00e9 des Sciences Pharmaceutiques, Universit\u00e9 de Bordeaux, 210 Chemin de Leysotte, 33140 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachid","family":"Ennamany","sequence":"additional","affiliation":[{"name":"Naolys, 86 Route d\u2019Arcachon, 33610 Cestas-Pierroton, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"M\u00e9rillon","sequence":"additional","affiliation":[{"name":"Polyphenols Biotech, Equipe Mol\u00e9cules d\u2019Int\u00e9r\u00eat Biologique, UMR 1366 INRAE, Facult\u00e9 des Sciences Pharmaceutiques, Universit\u00e9 de Bordeaux, 210 Chemin de Leysotte, 33140 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1051\/medsci\/2020223","article-title":"Vieillissement et int\u00e9grit\u00e9 de la peau. De la biologie cutan\u00e9e aux strat\u00e9gies anti-\u00e2ge","volume":"36","author":"Rorteau","year":"2020","journal-title":"M\u00e9decine\/Sciences"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Korkina, L.G., Mayer, W., and Chiara de Luca, C. (2017). Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin Rejuvenation. Biomolecules, 7.","DOI":"10.3390\/biom7020040"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chiocchio, H., Mandrone, M., Tomasi, P., Marincich, L., and Poli, F. (2021). Plant secondary metabolites: An opportunity for circular economy. Molecules, 26.","DOI":"10.3390\/molecules26020495"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.foodres.2018.02.045","article-title":"Plant cells as food\u2014A concept taking shape","volume":"107","author":"Nordlund","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_5","first-page":"330","article-title":"Natural products from plant cell cultures","volume":"Volume 65","author":"Petersen","year":"2008","journal-title":"Progress in Drug Research"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5483\/BMBRep.2016.49.3.264","article-title":"Plant cell culture strategies for the production of natural products","volume":"49","author":"Howat","year":"2016","journal-title":"BMB Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s00299-020-02592-2","article-title":"Plant cell cultures as food\u2014Aspects of sustainability and safety","volume":"39","author":"Nygren","year":"2020","journal-title":"Plant Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.copbio.2019.12.003","article-title":"Cellular agriculture\u2014Industrial biotechnology for food and materials","volume":"61","author":"Rischer","year":"2020","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Marchev, A.S., and Georgiev, M.I. (2020). Plant In Vitro Systems as a Sustainable Source of Active Ingredients for Cosmeceutical Application. Molecules, 25.","DOI":"10.3390\/molecules25092006"},{"key":"ref_10","first-page":"381","article-title":"Production of natural products by plant cell and organ cultures","volume":"39","author":"Alfermann","year":"2009","journal-title":"Annu. Plant Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8661","DOI":"10.1007\/s00253-018-9279-8","article-title":"Plant cell culture technology in the cosmetics and food industries: Current state and future trends","volume":"102","author":"Eibl","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18396","DOI":"10.3390\/ijms160818396","article-title":"Permeability study of polyphenols derived from a phenolic-enriched Hibiscus sabdariffa extract by UHPLC-ESI-UHR-Qq-TOF-MS","volume":"16","author":"Bermejo","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1002\/fsn3.2899","article-title":"Nutritional composition and phytochemical screening in different parts of Hibiscus syriacus L.","volume":"10","author":"Park","year":"2022","journal-title":"Food Sci. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104203","DOI":"10.1016\/j.jff.2020.104203","article-title":"Recent advances and possibilities for the use of plant phenolic compounds to manage ageing-related diseases","volume":"75","author":"Arruda","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/jocd.13093","article-title":"Polyphenols as natural antioxidants in cosmetics applications","volume":"19","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"620","DOI":"10.5530\/ijper.50.4.15","article-title":"Evaluation of Antioxidant, Toxicological and wound healing Properties of Hibiscus rosa-sinensis L. (Malvaceae) ethanolic leaves extract on different Experimental animal models","volume":"50","author":"Mondal","year":"2016","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103503","DOI":"10.1016\/j.arabjc.2021.103503","article-title":"Comparative analysis of phytochemical profile, antioxidant and anti-inflammatory activity from Hibiscus manihot L. flower","volume":"15","author":"Liu","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118722","DOI":"10.1016\/j.bbamcr.2020.118722","article-title":"Impact of intercellular crosstalk between epidermal keratinocytes and dermal fibroblasts on skin homeostasis","volume":"1867","author":"Kaessmeyer","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Russo, B., Brembilla, N.C., and Chizzolini, C. (2020). Interplay Between Keratinocytes and Fibroblasts: A Systematic Review Providing a New Angle for Understanding Skin Fibrotic Disorders. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00648"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e302","DOI":"10.1038\/emm.2016.167","article-title":"TMF and glycitin act synergistically on keratinocytes and fibroblasts to promote wound healing and anti-scarring activity","volume":"49","author":"Seo","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153276","DOI":"10.1016\/j.phymed.2020.153276","article-title":"Sulforaphane controls the release of paracrine factors by keratinocytes and thus mitigates particulate matter-induced premature skin aging by suppressing melanogenesis and maintaining collagen homeostasis","volume":"77","author":"Ko","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117985","DOI":"10.1016\/j.biopha.2025.117985","article-title":"Regulation of keratinocyte proliferation and differentiation by secoiridoid oleacein in monoculture and fibroblast co-culture models","volume":"185","author":"Cho","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1399-3054.1965.tb06874.x","article-title":"Organic growth factor requirements of tobacco tissue cultures","volume":"18","author":"Linsmaier","year":"1965","journal-title":"Physiol. Plant."},{"key":"ref_24","unstructured":"Ennamany, R., and M\u00e9rillon, J.M. (2003). Method for the Production of Phytoalexins. (Patent WO 03077880)."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/nar\/gkg034","article-title":"STRING: A database of predicted functional associations between proteins","volume":"31","author":"Huynen","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1021\/acs.jafc.6b01246","article-title":"Hibiscus sabdariffa (Roselle) extracts and wine: Phytochemical profile, physicochemical properties, and carbohydrase inhibition","volume":"64","author":"Ifie","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111708","DOI":"10.1016\/j.indcrop.2019.111708","article-title":"Effect of various solvents on the pulsed ultrasonic assisted extraction of T phenolic compounds from Hibiscus cannabinus L. leaves","volume":"140","author":"Sim","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Abdykerimova, S., Sakipova, Z., Nakonieczna, S., Koch, W., Biernasiuk, A., Grabarska, A., Malm, A., Kozhanova, K., and Kukula-Koch, W. (2020). Superior antioxidant capacity of Berberis iliensis\u2014HPLC-Q-TOF-MS based phytochemical studies and spectrophotometric determinations. Antioxidants, 9.","DOI":"10.3390\/antiox9060504"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6918","DOI":"10.1021\/jf5012825","article-title":"Isolation and structural elucidation of anthocyanidin 3,7-\u03b2-O-diglucosides and caffeoyl-glucaric acids from calafate berries","volume":"62","author":"Ruiz","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","first-page":"311","article-title":"Caffeoyl-D-glucaric acid derivatives in the genus Gnaphalium (Asteraceae: Gnaphalieae)","volume":"6","author":"Cicek","year":"2012","journal-title":"Rec. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, Z., Li, X., Jin, Y., Nan, T., Zhao, Y., Huang, L., and Yuan, Y. (2023). New evidence for Artemisia absinthium as an alternative to classical antibiotics: Chemical analysis of phenolic compounds, screening for antimicrobial activity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512044"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Olennikov, D.N., and Chirikova, N.K. (2024). Phenolic compounds of six unexplored Asteraceae species from Asia: Comparison of wild and cultivated plants. Horticulturae, 10.","DOI":"10.3390\/horticulturae10050486"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.fitote.2017.07.008","article-title":"Hydroxycinnamoyl derivatives and secoiridoid glycoside derivatives from Syringa vulgaris flowers and their effects on the pro-inflammatory responses of human neutrophils","volume":"121","author":"Dudek","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/pca.1325","article-title":"Investigations into the phenolic constituents of dog\u2019s mercury (Mercurialis perennis L.) by LC-MS\/MS and GC-MS analyses","volume":"23","author":"Lorenz","year":"2012","journal-title":"Phytochem. Anal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105864","DOI":"10.1016\/j.jff.2023.105864","article-title":"Argan pulp as a novel functional ingredient with beneficial effects on multiple metabolism biomarkers","volume":"110","author":"Martinez","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7741","DOI":"10.1021\/acs.jafc.4c11264","article-title":"Comprehensive analysis of phenolic compounds in Solanum glaucophyllum Desf","volume":"73","author":"Heymann","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2525\/ecb.61.73","article-title":"Conjugation of glucaric acid in comparison to quinic acid by caffeic acid allows for enhanced metabolite diversification in bush tea (Athrixia phylicoides DC.) extracts post UV light exposure","volume":"61","author":"Ramphinwa","year":"2023","journal-title":"Environ. Control Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104873","DOI":"10.1016\/j.bse.2024.104873","article-title":"Caffeoylhexaric acids in Inuleae: A case study of Geigeria alata, Inula helenium, and Telekia speciosa","volume":"116","author":"Stefanova","year":"2024","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_41","first-page":"317","article-title":"Chemical profiling and rapid discrimination of Blumea riparia and Blumea megacephala by UPLC-Q-Exactive-MS\/MS and HPLC","volume":"15","author":"Su","year":"2023","journal-title":"Chin. Herb. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13065-017-0262-8","article-title":"Highlighting mass spectrometric fragmentation differences and similarities between hydroxycinnamoyl-quinic acids and hydroxycinnamoyl-isocitric acids","volume":"11","author":"Masike","year":"2017","journal-title":"Chem. Cent. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2262203","DOI":"10.1080\/21655979.2023.2262203","article-title":"Performance of Malaysian kenaf Hibiscus cannabinus callus biomass and exopolysaccharide production in a novel liquid culture","volume":"14","author":"Norhisham","year":"2023","journal-title":"Bioengineered"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111572","DOI":"10.1016\/j.polymdegradstab.2025.111572","article-title":"Hydrogel biomaterials production through cell suspension culture of Hibiscus cannabinus in modified air-lift bioreactor for biomedical applications","volume":"241","author":"Usuldin","year":"2025","journal-title":"Polym. Degrad. Stab."},{"key":"ref_45","first-page":"45","article-title":"Production and enhancement of anthocyanin in callus line of roselle (Hibiscus sabdariffa L.)","volume":"2","author":"Abeda","year":"2014","journal-title":"Int. J. Recent Biotechnol."},{"key":"ref_46","first-page":"7932019","article-title":"Hibiscus syriacus extract from an established cell culture stimulates skin wound healing","volume":"2017","author":"Tito","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153870","DOI":"10.1016\/j.phymed.2021.153870","article-title":"Hibiscus syriacus L. cultivated in callus culture exerts cytotoxicity in colorectal cancer via Notch signaling-mediated cholesterol biosynthesis suppression","volume":"95","author":"Xu","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1111\/febs.12136","article-title":"The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly and signalling","volume":"280","author":"Schaefer","year":"2013","journal-title":"FEBS J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jtos.2023.06.013","article-title":"Small leucine-rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface","volume":"29","author":"Gesteira","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pang, X., Dong, N., and Zheng, Z. (2020). Small leucine-rich proteoglycans in skin wound healing. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01649"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1083\/jcb.141.5.1277","article-title":"Lumican regulates collagen fibril assembly: Skin fragility and corneal opacity in the absence of lumican","volume":"141","author":"Chakravarti","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.devcel.2020.06.039","article-title":"Essential functions of glycans in human epithelia dissected by a CRISPR-Cas9-engineered human organotypic skin model","volume":"54","author":"Dabelsteen","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1126\/science.abh1623","article-title":"Sphingolipids control dermal fibroblast heterogeneity","volume":"376","author":"Capolupo","year":"2022","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1365-2230.2004.01440.x","article-title":"The role of extracellular matrix protein 1 in human skin","volume":"29","author":"Chan","year":"2004","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1083\/jcb.201605119","article-title":"Glypican-6 promotes the growth of developing long bones by stimulating Hedgehog signaling","volume":"216","author":"Capurro","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1002\/pgr2.5","article-title":"Glypicans, 35 years later","volume":"1","author":"Filmus","year":"2023","journal-title":"Proteoglycan Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ydbio.2012.01.005","article-title":"Chondroitin sulfate synthase 1 (CHSY1) is required for bone development and digit patterning","volume":"363","author":"Wilson","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Huang, Y.F., Mizumoto, S., and Fujita, M. (2021). Novel insight into glycosaminoglycan biosynthesis based on gene expression profiles. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.709018"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrm2272","article-title":"Vacuolar ATPases: Rotary proton pumps in physiology and pathophysiology","volume":"8","author":"Forgac","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.devcel.2011.10.007","article-title":"Arl8 and SKIP act together to link lysosomes to kinesin-1","volume":"21","author":"Munro","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1074\/jbc.M311228200","article-title":"Endofin recruits TOM1 to endosomes","volume":"279","author":"Seet","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1002\/art.22084","article-title":"Insulin-like growth factor binding protein 5 induces skin fibrosis: A novel murine model for dermal fibrosis","volume":"54","author":"Yasuoka","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1042\/BST0370882","article-title":"IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response","volume":"37","author":"Sureshbabu","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1083\/jcb.132.1.239","article-title":"Extracellular matrix alters PDGF regulation of fibroblast integrins","volume":"132","author":"Xu","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.4081\/oncol.2012.e8","article-title":"An overview on the role of FLT3-tyrosine kinase receptor in acute myeloid leukemia: Biology and treatment","volume":"6","author":"Grafone","year":"2012","journal-title":"Oncol. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.0022-202X.2004.22719.x","article-title":"S100 proteins in the epidermis","volume":"123","author":"Eckert","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nri.2015.7","article-title":"Converging roles of caspases in inflammasome activation, cell death and innate immunity","volume":"16","author":"Man","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Macleod, T., Berekmeri, A., Bridgewood, C., Stacey, M., McGonagle, D., and Wittmann, M. (2021). The Immunological impact of IL-1 family cytokines on the epidermal barrier. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.808012"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/S0968-0004(02)02145-X","article-title":"A universal role for MyD88 in TLR\/IL-1R-mediated signaling","volume":"27","author":"Janssens","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1824624","DOI":"10.1155\/2019\/1824624","article-title":"The role of Toll-like receptors in skin host defense, psoriasis, and atopic dermatitis","volume":"2019","author":"Sun","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41580-019-0185-4","article-title":"Lysosomes as Dynamic Regulators of Cell and Organismal Homeostasis","volume":"21","author":"Ballabio","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-Spectrometric Exploration of Proteome Structure and Function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A Gene Network Regulating Lysosomal Biogenesis and Function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1243\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:51:13Z","timestamp":1787921473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":74,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091243"],"URL":"https:\/\/doi.org\/10.3390\/biom16091243","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}