{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:09:45Z","timestamp":1790096985325,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LIBON Inc.","award":["LIBON-2412-01"],"award-info":[{"award-number":["LIBON-2412-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Facial retaining ligaments maintain soft-tissue position and support the lower face, but whether fractional subnanosecond Nd:YAG laser treatment can improve the matrix architecture of ultraviolet (UV)-aged ligament tissue remains unclear. We evaluated whether laser-associated matrix alteration was accompanied by coordinated changes in LATS1-YAP-IQGAP1-NFAT1 signaling and collagen type I-dominant remodeling. Male Sprague\u2013Dawley rats were allocated to non-UV control, UV-aged, and UV-aged plus laser groups (n = 5 per group). After UV-aging induction, the laser group received a single fractional 1064 nm, 450 ps (subnanosecond) Nd:YAG treatment at 3.8 J\/cm2 and 10 Hz using a 6 \u00d7 6 mm spot, with a measured pulse energy of 1.07 J and a calculated irradiance of 8.44 GW\/cm2; 30 stacks, corresponding to 30 laser shots delivered to the same target area, were applied over 3 s. UV exposure increased cytosolic pLATS1\/LATS1, cytosolic pYAP, and ELISA-detected IQGAP1-associated pYAP signals while reducing nuclear YAP; laser treatment partially reversed these changes. Concurrently, laser treatment decreased ELISA-detected IQGAP1-associated pNFAT1 signals, restored nuclear NFAT1 localization, and reduced cytosolic pNFAT1. Quantitative immunofluorescence, histomorphometric, and ultrastructural analyses showed restoration of the collagen type I signal and collagen type I\/III ratio and improvements in collagen density, coherency, angular deviation, and collagen bundle diameter. Laser treatment restored the expression of tendon\/ligament-lineage markers, including scleraxis, mohawk homeobox, and tenomodulin; UV-induced elevations in osteogenic markers (RUNX2, SP7, and ALPL) were not significantly attenuated. Overall, fractional subnanosecond Nd:YAG laser treatment partially improved the matrix architecture of UV-aged rat facial retaining ligaments. These exploratory findings support an association model linking laser-associated matrix remodeling with coordinated changes in LATS1-YAP-IQGAP1-NFAT1 signaling, lineage-marker recovery, and collagen type I-dominant realignment, but do not establish a causal signaling sequence or functional mechanical strengthening.<\/jats:p>","DOI":"10.3390\/ijms27188371","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fractional\u00a0Subnanosecond\u00a0Nd:YAG Laser Improves Matrix Architecture in Ultraviolet-Aged Facial Retaining Ligaments in Rats"],"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"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Geebum","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":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Misogain Dermatology Clinic, Gimpo 10108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9042-7388","authenticated-orcid":false,"given":"Myungjune","family":"Oh","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, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Gangnam ON Clinic, Seoul 06129, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Seung Min","family":"Oh","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, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Gangnam ON Clinic, Seoul 06129, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Min Seung","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":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Inee Clinic, Seoul 06030, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2683-2606","authenticated-orcid":false,"given":"Jae Ik","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, International Healthcare Center, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"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"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"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, College of Medicine, Gachon University, 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"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/00006534-198901000-00003","article-title":"The retaining ligaments of the cheek","volume":"83","author":"Furnas","year":"1989","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1177\/1090820X13495405","article-title":"Retaining ligaments of the face: Review of anatomy and clinical applications","volume":"33","author":"Alghoul","year":"2013","journal-title":"Aesthetic Surg. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.cps.2008.02.003","article-title":"Surgical anatomy of the midcheek: Facial layers, spaces, and the midcheek segments","volume":"35","author":"Mendelson","year":"2008","journal-title":"Clin. Plast. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1001\/archfaci.2011.1533","article-title":"Biomechanical properties of the facial retaining ligaments","volume":"14","author":"Brandt","year":"2012","journal-title":"Arch. Facial Plast. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/379335a0","article-title":"Molecular basis of sun-induced premature skin ageing and retinoid antagonism","volume":"379","author":"Fisher","year":"1996","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0002-9440(10)63337-8","article-title":"Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor\/Smad signaling","volume":"165","author":"Quan","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/acel.12265","article-title":"Age-associated reduction of cellular spreading\/mechanical force up-regulates matrix metalloproteinase-1 expression and collagen fibril fragmentation via c-Jun\/AP-1 in human dermal fibroblasts","volume":"13","author":"Qin","year":"2014","journal-title":"Aging Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00795-019-00224-7","article-title":"Ultrastructure and three-dimensional architecture of the anterior cruciate ligament in the knee joints of young and old monkeys","volume":"53","author":"Kaku","year":"2020","journal-title":"Med. Mol. Morphol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/joa.13125","article-title":"Age-related changes of tendon fibril micro-morphology and gene expression","volume":"236","author":"Ribitsch","year":"2020","journal-title":"J. Anat."},{"key":"ref_10","first-page":"425","article-title":"Scar formation and ligament healing","volume":"41","author":"Hildebrand","year":"1998","journal-title":"Can. J. Surg."},{"key":"ref_11","first-page":"265","article-title":"Collagen in tendon, ligament, and bone healing. A current review","volume":"318","author":"Liu","year":"1995","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/lsm.22655","article-title":"In vivo multiphoton-microscopy of picosecond-laser-induced optical breakdown in human skin","volume":"49","author":"Balu","year":"2017","journal-title":"Lasers Surg. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10103-022-03704-y","article-title":"An update on fractional picosecond laser treatment: Histology and clinical applications","volume":"38","author":"Zhou","year":"2023","journal-title":"Lasers Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e70307","DOI":"10.1111\/jocd.70307","article-title":"The Comparison of the Efficacy and Safety of Fractional 1064\u2009nm Nd:YAG Picosecond Laser and Fractional Q-Switched 1064-nm Nd:YAG Laser in the Improvement of Photoaging: A Split-Face Study","volume":"24","author":"Tang","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1101\/gad.1843810","article-title":"A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)","volume":"24","author":"Zhao","year":"2010","journal-title":"Genes. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"502","DOI":"10.5483\/BMBRep.2023-0059","article-title":"Photobiomodulation therapy activates YAP and triggers proliferation and dedifferentiation of M\u00fcller glia in mammalian retina","volume":"56","author":"Kim","year":"2023","journal-title":"BMB Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bednarski, I.A., Dr\u00f3\u017cd\u017c, I., Ci\u0105\u017cy\u0144ska, M., W\u00f3dz, K., Narbutt, J., and Lesiak, A. (2025). Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes-Preliminary Study. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030596"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/art.42460","article-title":"Regulation of Photosensitivity by the Hippo Pathway in Lupus Skin","volume":"75","author":"Hile","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19261","DOI":"10.1074\/jbc.M116.732529","article-title":"IQGAP1 Binds to Yes-associated Protein (YAP) and Modulates Its Transcriptional Activity","volume":"291","author":"Sayedyahossein","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11381","DOI":"10.1073\/pnas.1019711108","article-title":"Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex","volume":"108","author":"Sharma","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e20200053","DOI":"10.1084\/jem.20200053","article-title":"Mechanosensing through YAP controls T cell activation and metabolism","volume":"217","author":"Meng","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17665","DOI":"10.1074\/jbc.M610113200","article-title":"Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts","volume":"282","author":"Brideau","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1038\/s41598-018-21194-3","article-title":"Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes","volume":"8","author":"Shukunami","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/stem.1866","article-title":"Mohawk promotes the tenogenesis of mesenchymal stem cells through activation of the TGF\u03b2 signaling pathway","volume":"33","author":"Liu","year":"2015","journal-title":"Stem Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1002\/art.38020","article-title":"Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation","volume":"65","author":"Nakahara","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eabb2233","DOI":"10.1126\/scitranslmed.abb2233","article-title":"A self-amplifying loop of YAP and SHH drives formation and expansion of heterotopic ossification","volume":"13","author":"Cong","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1111\/jcmm.15240","article-title":"Heterotopic ossification of tendon and ligament","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/jcmm.13972","article-title":"TRPV4 regulates matrix stiffness and TGF\u03b21-induced epithelial-mesenchymal transition","volume":"23","author":"Sharma","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101839","DOI":"10.1016\/j.jbc.2022.101839","article-title":"Calmodulin activates the Hippo signaling pathway by promoting LATS1 kinase-mediated inhibitory phosphorylation of the transcriptional coactivator YAP","volume":"298","author":"Thines","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1093\/nar\/gkac189","article-title":"Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway","volume":"50","author":"Jin","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature14228","article-title":"A gp130-Src-YAP module links inflammation to epithelial regeneration","volume":"519","author":"Taniguchi","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9661","DOI":"10.1039\/C7RA12693J","article-title":"Coherency image analysis to quantify collagen architecture: Implications in scar assessment","volume":"8","author":"Clemons","year":"2018","journal-title":"RSC Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-3-319-28549-8_3","article-title":"Transforms and Operators for Directional Bioimage Analysis: A Survey","volume":"219","author":"Storath","year":"2016","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jmbbm.2011.08.016","article-title":"Characterization of the anisotropic mechanical properties of excised human skin","volume":"5","author":"Destrade","year":"2012","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1098\/rsif.2011.0727","article-title":"Determination of the layer-specific distributed collagen fibre orientations in human thoracic and abdominal aortas and common iliac arteries","volume":"9","author":"Schriefl","year":"2012","journal-title":"J. R. Soc. Interface"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1111\/os.13279","article-title":"Effectiveness of Platelet-Rich Plasma in Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials","volume":"14","author":"Cao","year":"2022","journal-title":"Orthop. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4137\/CMAMD.S39160","article-title":"A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain","volume":"9","author":"Hauser","year":"2016","journal-title":"Clin. Med. Insights Arthritis Musculoskelet. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"503","DOI":"10.2174\/1574888X17666220127111135","article-title":"Stem Cells in Tendon Regeneration and Factors governing Tenogenesis","volume":"17","author":"Ding","year":"2022","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"NP979","DOI":"10.1093\/asj\/sjad235","article-title":"Age-Related Changes of the Zygomatic Ligament: An Experimental Animal Study","volume":"43","author":"Zhang","year":"2023","journal-title":"Aesthetic Surg. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mu, J., Ma, H., Chen, H., Zhang, X., and Ye, M. (2021). Luteolin Prevents UVB-Induced Skin Photoaging Damage by Modulating SIRT3\/ROS\/MAPK Signaling: An in vitro and in vivo Studies. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.728261"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Byun, K.-A., Lee, J.I., Oh, S., Kim, S.E., Seo, S.B., Son, K.H., and Byun, K. (2026). Pulsed Electromagnetic Field Exposure Attenuates Ultraviolet B-Induced Dermal Collagen Loss in Association with A2A Adenosine Receptor Signaling. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27177904"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:31:15Z","timestamp":1790094675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":43,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188371"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188371","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}