{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:10:47Z","timestamp":1787314247558,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Scleral tissue is a connective tissue made up of dense, intertwined collagen fibers that plays a vital part in preserving both the integrity of vision and the shape of the eyeball. Numerous studies have been conducted on the impact of terahertz radiation on biological systems. Terahertz radiation can affect cell morphology and function by mediating modifications in protein conformation and gene expression, according to recent research. Though terahertz waves found in the environment directly expose scleral tissue, little is known about how terahertz radiation affects scleral fibroblasts biologically. In this work, we investigated how 0.1 THz radiation affected the global expression levels of proteins and the viability of human fetal scleral fibroblasts (HFSFs). A total of 79.44% of the differentially expressed proteins (DEPs) showed significant downregulation in expression levels after 60 min of exposure to terahertz radiation. Enrichment analysis of DEPs revealed that terahertz radiation enhanced the expression of cytoskeletal keratins, disrupted supercoplexes\u2019 assembly, and impaired mitochondrial respiration. Moreover, terahertz radiation influences the remodeling process of the scleral extracellular matrix by triggering the TGF-\u03b2\/Smad signaling pathway. Changes in transcriptional activity of several extracellular matrix (ECM)-related genes persisted for 12 h in the absence of terahertz radiation. Research findings indicate that 0.1 THz radiation is capable of disrupting the dynamic balance between collagen synthesis and degradation in scleral fibroblasts. Such an imbalance may induce alterations in the structural integrity and biomechanical properties of the sclera, thereby elevating the potential risk of myopia onset or progression.<\/jats:p>","DOI":"10.3390\/cells14191512","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T10:49:34Z","timestamp":1759142974000},"page":"1512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Using 0.1 THz Radiation Regulates Collagen Synthesis Through TGF-\u03b2\/Smad Signaling Pathway in Human Fetal Scleral Fibroblasts"],"prefix":"10.3390","volume":"14","author":[{"given":"Wenxia","family":"Wang","sequence":"first","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Sun","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6146-1139","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwu","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuocheng","family":"She","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pandeng","family":"Hou","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxia","family":"He","sequence":"additional","affiliation":[{"name":"The Center for Terahertz Waves, School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1023\/A:1024420104400","article-title":"THz-Spectroscopy of Biological Molecules","volume":"29","author":"Globus","year":"2003","journal-title":"J. Biol. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.tibtech.2016.04.008","article-title":"Biomedical Applications of Terahertz Spectroscopy and Imaging","volume":"34","author":"Yang","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nikitkina, A.I., Bikmulina, P.Y., Gafarova, E.R., Kosheleva, N.V., Efremov, Y.M., Bezrukov, E.A., Butnaru, D.V., Dolganova, I.N., Chernomyrdin, N.V., and Cherkasova, O.P. (2021). Terahertz radiation and the skin: A review. J. Biomed. Opt., 26.","DOI":"10.1117\/1.JBO.26.4.043005"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.mrgentox.2015.06.003","article-title":"Biological effects of in vitro THz radiation exposure in human foetal fibroblasts","volume":"793","author":"Franchini","year":"2015","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/em.22192","article-title":"Study of the effects of 0.15 terahertz radiation on genome integrity of adult fibroblasts","volume":"59","author":"Franchini","year":"2018","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/lsm.20960","article-title":"In vitro investigation of the biological effects associated with human dermal fibroblasts exposed to 2.52 THz radiation","volume":"43","author":"Wilmink","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1007\/s10762-011-9794-5","article-title":"Invited Review Article: Current State of Research on Biological Effects of Terahertz Radiation","volume":"32","author":"Wilmink","year":"2011","journal-title":"J. Infrared Millim. Terahertz Waves"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, K.T., Park, J., Jo, S.J., Jung, S., Kwon, O.S., Gallerano, G.P., Park, W.Y., and Park, G.S. (2013). High-power femtosecond-terahertz pulse induces a wound response in mouse skin. Sci. Rep., 3.","DOI":"10.1038\/srep02296"},{"key":"ref_9","first-page":"96","article-title":"Investigation of the effect of terahertz radiation on acute wounds in mice","volume":"36","author":"Lin","year":"2025","journal-title":"Chin. J. Aesthetic Plast. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e35313","DOI":"10.1016\/j.heliyon.2024.e35313","article-title":"Collagen is crucial target protein for scleral remodeling and biomechanical change in myopia progression and control","volume":"10","author":"Sun","year":"2024","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.molimm.2024.01.011","article-title":"The role of transforming growth factor beta in myopia development","volume":"167","author":"Ku","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1364\/JOSAB.19.001476","article-title":"Terahertz dielectric properties of polystyrene foam","volume":"19","author":"Zhao","year":"2002","journal-title":"J. Opt. Soc. Am. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s10762-016-0341-2","article-title":"A Free-Space Measurement Technique of Terahertz Dielectric Properties","volume":"38","author":"Zhang","year":"2016","journal-title":"J. Infrared Millim. Terahertz Waves"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1089\/dna.2019.5220","article-title":"Deregulated Mitochondrial DNA in Diseases","volume":"39","author":"Nguyen","year":"2020","journal-title":"DNA Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109391","DOI":"10.1016\/j.isci.2024.109391","article-title":"0.263 terahertz irradiation induced genes expression changes in Caenorhabditis elegans","volume":"27","author":"Shang","year":"2024","journal-title":"iScience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s10762-018-0512-4","article-title":"Topology-Based Prediction of Pathway Dysregulation Induced by Intense Terahertz Pulses in Human Skin Tissue Models","volume":"39","author":"Hough","year":"2018","journal-title":"J. Infrared Millim. Terahertz Waves"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106818","DOI":"10.1016\/j.phrs.2023.106818","article-title":"Targeting the KRT16-vimentin axis for metastasis in lung cancer","volume":"193","author":"Wang","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.expneurol.2016.10.011","article-title":"Identification of KRT16 as a target of an autoantibody response in complex regional pain syndrome","volume":"287","author":"Tajerian","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1167\/iovs.64.3.27","article-title":"Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization","volume":"64","author":"Vergouwen","year":"2023","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6089","DOI":"10.1167\/iovs.16-19563","article-title":"Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse","volume":"57","author":"Metlapally","year":"2016","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8627","DOI":"10.3390\/cimb46080508","article-title":"Keratins 6, 16, and 17 in Health and Disease: A Summary of Recent Findings","volume":"46","author":"Romashin","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ijbiomac.2022.04.216","article-title":"Keratin-based wound dressings: From waste to wealth","volume":"211","author":"Ye","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pecoraro, A., Pagano, M., Russo, G., and Russo, A. (2021). Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115496"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bogomazova, A.N., Vassina, E.M., Goryachkovskaya, T.N., Popik, V.M., Sokolov, A.S., Kolchanov, N.A., Lagarkova, M.A., Kiselev, S.L., and Peltek, S.E. (2015). No DNA damage response and negligible genome-wide transcriptional changes in human embryonic stem cells exposed to terahertz radiation. Sci. Rep., 5.","DOI":"10.1038\/srep07749"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1364\/BOE.426928","article-title":"0.1 THz exposure affects primary hippocampus neuron gene expression via alternating transcription factor binding","volume":"12","author":"Shang","year":"2021","journal-title":"Biomed. Opt. Express"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1364\/BOE.528706","article-title":"Membrane-mediated modulation of mitochondrial physiology by terahertz waves","volume":"15","author":"Lei","year":"2024","journal-title":"Biomed. Opt. Express"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Marchesi, N., Fahmideh, F., Boschi, F., Pascale, A., and Barbieri, A. (2021). Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas. Cells, 10.","DOI":"10.3390\/cells10092394"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100084-1","DOI":"10.59717\/j.xinn-life.2024.100084","article-title":"Terahertz technology: A new frontier in Alzheimer\u2019s disease therapy","volume":"2","author":"Zhang","year":"2024","journal-title":"Innov. Life"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s12264-023-01145-3","article-title":"Terahertz Irradiation Improves Cognitive Impairments and Attenuates Alzheimer\u2019s Neuropathology in the APPSWE\/PS1DE9 Mouse: A Novel Therapeutic Intervention for Alzheimer\u2019s Disease","volume":"40","author":"Zhang","year":"2023","journal-title":"Neurosci. Bull."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bmt.2024.06.001","article-title":"Proteomic insights into myopia development: Differential protein expression and the role of calcium signaling in form deprivation myopia in Guinea pigs","volume":"7","author":"Liang","year":"2024","journal-title":"Biomed. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1167\/iovs.64.13.15","article-title":"Integrative Transcriptome and Proteome Analyses Elucidate the Mechanism of Lens-Induced Myopia in Mice","volume":"64","author":"Ji","year":"2023","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4252\/wjsc.v4.i5.28","article-title":"Different roles of TGF-\u03b2 in the multi-lineage differentiation of stem cells","volume":"4","author":"Wang","year":"2012","journal-title":"World J. Stem Cells"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dione, M.N., Zhang, Q., Shang, S., and Lu, X. (2024). Transcriptomic Analysis of Blood Collagen-Induced Arthritis Mice Exposed to 0.1 THz Reveals Inhibition of Genes and Pathways Involved in Rheumatoid Arthritis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312812"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/emboj\/19.8.1745","article-title":"Transcriptional control by the TGF-beta\/Smad signaling system","volume":"19","author":"Wotton","year":"2000","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-\u03b2 Signaling from Cell Membrane to the Nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e29961","DOI":"10.1097\/MD.0000000000029961","article-title":"Association between TGF-\u03b2 gene polymorphism and myopia: A systematic review and meta-analysis","volume":"101","author":"Zhu","year":"2022","journal-title":"Medicine"},{"key":"ref_37","first-page":"885","article-title":"Suppression of type I collagen in human scleral fibroblasts treated with extremely low-frequency electromagnetic fields","volume":"19","author":"Wang","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1167\/iovs.09-3460","article-title":"Inhibition of Human Scleral Fibroblast Cell Attachment to Collagen Type I by TGFBIp","volume":"50","author":"Shelton","year":"2009","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbrc.2022.12.009","article-title":"Ultraviolet A at levels experienced outdoors suppresses transforming growth factor-beta signaling and collagen production in human scleral fibroblasts","volume":"641","author":"Hsiao","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18121","DOI":"10.1074\/jbc.M400381200","article-title":"Isoform-specific Changes in Scleral Transforming Growth Factor-\u03b2 Expression and the Regulation of Collagen Synthesis during Myopia Progression","volume":"279","author":"Jobling","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5126560","DOI":"10.1155\/2016\/5126560","article-title":"Expression of Wnt\/\u03b2-Catenin Signaling Pathway and Its Regulatory Role in Type I Collagen with TGF-\u03b21 in Scleral Fibroblasts from an Experimentally Induced Myopia Guinea Pig Model","volume":"2016","author":"Li","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109023","DOI":"10.1016\/j.exer.2022.109023","article-title":"Hsa-miR-142-3p reduces collagen I in human scleral fibroblasts by targeting TGF-\u03b21 in high myopia","volume":"219","author":"Li","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_43","first-page":"1153","article-title":"Steady state mRNA levels in tree shrew sclera with form-deprivation myopia and during recovery","volume":"42","author":"Siegwart","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/19\/1512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:08:39Z","timestamp":1759144119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/19\/1512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["cells14191512"],"URL":"https:\/\/doi.org\/10.3390\/cells14191512","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]}}}