{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:27:22Z","timestamp":1786616842684,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin \u03b21 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-\u03b2 (TGF-\u03b2)\/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell\u2013matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling.<\/jats:p>","DOI":"10.3390\/molecules31162820","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:31:09Z","timestamp":1786613469000},"page":"2820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silk Fibroin Peptides Promote Extracellular Matrix Homeostasis in Photoaging via Modulation of the ITGB1\/FAK-TGF-\u03b2\/Smad Signaling Axis"],"prefix":"10.3390","volume":"31","author":[{"given":"Siyuan","family":"He","sequence":"first","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiu","family":"Yan","sequence":"additional","affiliation":[{"name":"Zhejiang Daldrem Biotechnology Co., Ltd., Ningbo 315153\u200c, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Zhejiang Daldrem Biotechnology Co., Ltd., Ningbo 315153\u200c, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Diao","sequence":"additional","affiliation":[{"name":"Zhejiang Daldrem Biotechnology Co., Ltd., Ningbo 315153\u200c, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhuai","family":"Jia","sequence":"additional","affiliation":[{"name":"Zhejiang Daldrem Biotechnology Co., Ltd., Ningbo 315153\u200c, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-8927","authenticated-orcid":false,"given":"Xiaodong","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, M., Lin, Y., Han, Z., Huang, X., Zhou, S., Wang, S., Zhou, Y., Han, X., and Chen, H. (2024). Exploring mechanisms of skin aging: Insights for clinical treatment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1421858"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.jid.2020.12.011","article-title":"Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms","volume":"141","author":"Krutmann","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e70309","DOI":"10.1111\/srt.70309","article-title":"Establishing an Improved Cellular Photoaging Model by Repeated UVA Exposure of Human Skin Fibroblasts","volume":"31","author":"Tang","year":"2025","journal-title":"Ski. Res. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13008-024-00107-z","article-title":"Role of reactive oxygen species in ultraviolet-induced photodamage of the skin","volume":"19","author":"Wei","year":"2024","journal-title":"Cell Div."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s12964-024-01663-1","article-title":"Molecular mechanisms of aging and anti-aging strategies","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhou, F., Nie, G., Li, L., Wen, J., He, S., and Yao, A. (2025). 3D-cultured hADSCs-derived exosomes deliver circ_0011129 to synergistically attenuate skin photoaging. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1627472"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gao, H., Shi, J., Li, G., Lai, Z., Liu, Y., Yuan, C., and Mei, W. (2025). Camellia japonica Flower Extract and the Active Constituent Hyperoside Repair DNA Damage Through FUNDC1-Mediated Mitophagy Pathway for Skin Anti-Aging. Antioxidants, 14.","DOI":"10.3390\/antiox14080968"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nan, L., Guo, P., Hui, W., Xia, F., and Yi, C. (2025). Recent advances in dermal fibroblast senescence and skin aging: Unraveling mechanisms and pioneering therapeutic strategies. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1592596"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1136\/ard-2023-224129","article-title":"Ablation of integrin-mediated cell\u2013collagen communication alleviates fibrosis","volume":"82","author":"Sawant","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41580-019-0134-2","article-title":"Integrins as biomechanical sensors of the microenvironment","volume":"20","author":"Kechagia","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"C415","DOI":"10.1152\/ajpcell.00013.2017","article-title":"Expression of CTGF\/CCN2 in response to LPA is stimulated by fibrotic extracellular matrix via the integrin\/FAK axis","volume":"314","author":"Contreras","year":"2018","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1083\/jcb.200608010","article-title":"Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics","volume":"176","author":"Schober","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/embor.2009.276","article-title":"Integrin\u2013TGF-\u03b2 crosstalk in fibrosis, cancer and wound healing","volume":"11","author":"Margadant","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yeung, V., Sriram, S., Tran, J.A., Guo, X., Hutcheon, A.E.K., Zieske, J.D., Karamichos, D., and Ciolino, J.B. (2021). FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro. Biomolecules, 11.","DOI":"10.3390\/biom11111682"},{"key":"ref_15","first-page":"75","article-title":"Bioactive peptides and proteins for tissue repair: Microenvironment modulation, rational delivery, and clinical potential","volume":"11","author":"Hao","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2409739","DOI":"10.1002\/smll.202409739","article-title":"Cellular Interactions and Biological Effects of Silk Fibroin: Implications for Tissue Engineering and Regenerative Medicine","volume":"21","author":"Zhu","year":"2025","journal-title":"Small"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105087","DOI":"10.1016\/j.jddst.2023.105087","article-title":"Anti-aging peptides for advanced skincare: Focus on nanodelivery systems","volume":"89","author":"Veiga","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1080\/10717544.2022.2096717","article-title":"Enhanced transdermal insulin basal release from silk fibroin (SF) hydrogels via iontophoresis","volume":"29","author":"Sakunpongpitiporn","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.34133\/research.1255","article-title":"A Silk-Derived Dual Peptide System Suppresses Skin Photoaging by Inhibiting PDGFR\u03b2-Mediated Cellular Senescence and TRPV4-Mediated Melanogenesis","volume":"9","author":"Sun","year":"2026","journal-title":"Research"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103307","DOI":"10.1016\/j.redox.2024.103307","article-title":"Unravelling the antioxidant behaviour of self-assembly \u03b2-Sheet in silk fibroin","volume":"76","author":"Qian","year":"2024","journal-title":"Redox Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Han, S., Ballinger, E., Choung, S.-Y., and Kwon, J. (2022). Anti-Photoaging Effect of Hydrolysates from Pacific Whiting Skin via MAPK\/AP-1, NF-\u03baB, TGF-\u03b2\/Smad, and Nrf-2\/HO-1 Signaling Pathway in UVB-Induced Human Dermal Fibroblasts. Mar. Drugs, 20.","DOI":"10.3390\/md20050308"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xu, Q., Hou, W., Zheng, Y., Liu, C., Gong, Z., Lu, C., Lai, W., and Maibach, H.I. (2014). Ultraviolet A-Induced Cathepsin K Expression Is Mediated via MAPK\/AP-1 Pathway in Human Dermal Fibroblasts. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102732"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104544","DOI":"10.1016\/j.jff.2021.104544","article-title":"Protective effects of LPL-EPS-02 on human dermal fibroblasts damaged by UVA radiation","volume":"83","author":"Sun","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Martins, S.G., Zilh\u00e3o, R., Thorsteinsd\u00f3ttir, S., and Carlos, A.R. (2021). Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.673002"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41419-026-08679-0","article-title":"LMO7-mediated POLR2A degradation promotes cellular senescence through the MDM4\/p53\/p21 axis","volume":"17","author":"Lai","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3892\/ijmm.2014.1815","article-title":"Protective effect of porphyra-334 on UVA-induced photoaging in human skin fibroblasts","volume":"34","author":"Ryu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/jidsymp.2009.8","article-title":"Matrix-Degrading Metalloproteinases in Photoaging","volume":"14","author":"Quan","year":"2009","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103102","DOI":"10.1016\/j.mtbio.2026.103102","article-title":"A multifunctional nano-hydrogel attenuates skin photoaging via regulating ECM microenvironment homeostasis","volume":"38","author":"Wang","year":"2026","journal-title":"Mater. Today Bio"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13259","DOI":"10.1021\/ja212170b","article-title":"Conformational Dynamics Accompanying the Proteolytic Degradation of Trimeric Collagen I by Collagenases","volume":"134","author":"Adhikari","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eadw6425","DOI":"10.1126\/sciadv.adw6425","article-title":"Mechanochemical waves in focal adhesions during cell migration","volume":"11","author":"Marquez","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"140445","DOI":"10.1016\/j.jcis.2026.140445","article-title":"Nanoarchitectonics of peptide-silk fibroin hydrogel as a cell reservoir for volumetric muscle loss therapy","volume":"717","author":"Liu","year":"2026","journal-title":"J. Colloid Interface Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00914","DOI":"10.1002\/adhm.202500914","article-title":"Cell Surface Thiol Engineering Mechanoregulates Myogenic Differentiation via the FAK\u2013PI3K\u2013AKT Axis","volume":"15","author":"Kim","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12647","DOI":"10.1039\/D6SC01417H","article-title":"Rethinking photosensitization in therapy and sun protection","volume":"17","author":"Bastos","year":"2026","journal-title":"Chem. Sci."},{"key":"ref_34","first-page":"666","article-title":"Silk Fibroin Counteracts Fibroblast Senescence to Restore ECM Homeostasis in Aged Skin","volume":"58","author":"Cheng","year":"2026","journal-title":"Bioact. Mater."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/16\/2820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:31:30Z","timestamp":1786613490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/16\/2820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":34,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["molecules31162820"],"URL":"https:\/\/doi.org\/10.3390\/molecules31162820","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}