{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T20:38:11Z","timestamp":1782419891512,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP16K11366"],"award-info":[{"award-number":["JP16K11366"]}]},{"name":"JSPS KAKENHI","award":["18H02961"],"award-info":[{"award-number":["18H02961"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is unclear whether normal human skin tissue or abnormal scarring are photoreceptive. Therefore, this study investigated photosensitivity in normal skin tissue and hypertrophic scars. The expression of opsins, which are photoreceptor proteins, in normal dermal fibroblasts (NDFs) and hypertrophic scar fibroblasts (HSFs) was examined. After exposure to blue light (BL), changes in the expression levels of \u03b1SMA and clock-related genes, specifically PER2 and BMAL1, were examined in both fibroblast types. Opsins were expressed in both fibroblast types, with OPN3 exhibiting the highest expression levels. After peripheral circadian rhythm disruption, BL induced rhythm formation in NDFs. In contrast, although HSFs showed changes in clock-related gene expression levels, no distinct rhythm formation was observed. The expression level of \u03b1SMA was significantly higher in HSFs and decreased to the same level as that in NDFs upon BL exposure. When OPN3 knocked-down HSFs were exposed to BL, the reduction in \u03b1SMA expression was inhibited. This study showed that BL exposure directly triggers peripheral circadian synchronization in NDFs but not in HSFs. OPN3-mediated BL exposure inhibited HSFs. Although the current results did not elucidate the relationship between peripheral circadian rhythms and hypertrophic scars, they show that BL can be applied for the prevention and treatment of hypertrophic scars and keloids.<\/jats:p>","DOI":"10.3390\/ijms25042126","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T11:42:05Z","timestamp":1707478925000},"page":"2126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Differential Photosensitivity of Fibroblasts Obtained from Normal Skin and Hypertrophic Scar Tissues"],"prefix":"10.3390","volume":"25","author":[{"given":"Junya","family":"Kusumoto","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"},{"name":"Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Terashi","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-4549","authenticated-orcid":false,"given":"Shunsuke","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1097\/00006534-199910000-00031","article-title":"On the nature of hypertrophic scars and keloids: A review","volume":"104","author":"Niessen","year":"1999","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1097\/01.mop.0000236389.41462.ef","article-title":"Keloids and scars: A review of keloids and scars, their pathogenesis, risk factors, and management","volume":"18","author":"Slemp","year":"2006","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1006\/cbir.1995.1090","article-title":"Factors influencing myofibroblast differentiation during wound healing and fibrosis","volume":"19","author":"Desmouliere","year":"1995","journal-title":"Cell. Biol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2119\/molmed.2009.00153","article-title":"Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies","volume":"17","author":"Gauglitz","year":"2011","journal-title":"Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23259","DOI":"10.3390\/ijms161023259","article-title":"Topical PDT in the treatment of benign skin diseases: Principles and new application","volume":"16","author":"Kim","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_6","first-page":"882","article-title":"Phototherapy: Theory and practice","volume":"21","author":"Kurz","year":"2023","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1524-475X.2012.00771.x","article-title":"Green light emitting diodes accelerate wound healing: Characterization of the effect and its molecular basis in vitro and in vivo","volume":"20","author":"Fushimi","year":"2012","journal-title":"Wound Repair Regen."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/lsm.22316","article-title":"Visible red light enhances physiological anagen entry in vivo and has direct and indirect stimulative effects in vitro","volume":"47","author":"Sheen","year":"2015","journal-title":"Lasers Surg. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Uzunbajakava, N.E., Tobin, D.J., Botchkareva, N.V., Dierickx, C., Bjerring, P., and Town, G. (2023). Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations. J. Biophotonics, 16.","DOI":"10.1002\/jbio.202200257"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev-vision-100820-094018","article-title":"An expanding role for nonvisual opsins in extraocular light sensing physiology","volume":"9","author":"Andrabi","year":"2023","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1098\/rstb.2009.0051","article-title":"Evolution of opsins and phototransduction","volume":"364","author":"Shichida","year":"2009","journal-title":"Philo. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10571-020-00997-x","article-title":"Non-visual opsins and novel photo-detectors in the vertebrate inner retina mediate light responses within the blue spectrum region","volume":"42","author":"Guido","year":"2022","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/bjd.18410","article-title":"Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human dermal fibroblast cells","volume":"182","author":"Lan","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Olinski, L.E., Lin, E.M., and Oancea, E. (2020). Illuminating insights into opsin 3 function in the skin. Adv. Biol. Regul., 75.","DOI":"10.1016\/j.jbior.2019.100668"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/gtc.12751","article-title":"OPN4 belongs to the photosensitive system of the human skin","volume":"25","author":"Kusumoto","year":"2020","journal-title":"Genes Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1126\/science.1067262","article-title":"Phototransduction by retinal ganglion cells that set the circadian clock","volume":"295","author":"Berson","year":"2002","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1126\/science.1076701","article-title":"Role of melanopsin in circadian responses to light","volume":"298","author":"Ruby","year":"2002","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1126\/science.1076848","article-title":"Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting","volume":"298","author":"Panda","year":"2002","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1069609","article-title":"Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity","volume":"295","author":"Hattar","year":"2002","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1046\/j.1523-1747.2000.00121.x","article-title":"Expression of the circadian clock genes clock and period1 in human skin","volume":"115","author":"Zanello","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2004.11.015","article-title":"Circadian gene expression in individual fibroblasts: Cell-autonomous and self-sustained oscillators pass time to daughter cells","volume":"119","author":"Nagoshi","year":"2004","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nature00965","article-title":"Coordination of circadian timing in mammals","volume":"418","author":"Reppert","year":"2002","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1093\/nar\/gkt307","article-title":"Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm","volume":"41","author":"Cheon","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17582","DOI":"10.1073\/pnas.0909733106","article-title":"Glucocorticoid regulation of the circadian clock modulates glucose homeostasis","volume":"106","author":"So","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Matsui, M.S., Pelle, E., Dong, K., and Pernodet, N. (2016). Biological rhythms in the skin. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060801"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/jid.2013.366","article-title":"A meeting of two chronobiological systems: Circadian proteins period1 and BMAL1 modulate the human hair cycle clock","volume":"134","author":"Hardman","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1000951","DOI":"10.3389\/fimmu.2022.1000951","article-title":"Potential effects of shift work on skin autoimmune diseases","volume":"13","author":"Stenger","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1016\/j.cub.2019.08.063","article-title":"Neuropsin (OPN5) mediates local light-dependent induction of circadian clock genes and circadian photoentrainment in exposed murine skin","volume":"29","author":"Buhr","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/lsm.20952","article-title":"Prophylactic low-level light therapy for the treatment of hypertrophic scars and keloids: A case series","volume":"42","author":"Barole","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.288.5466.682","article-title":"Resetting central and peripheral circadian oscillators in transgenic rats","volume":"288","author":"Yamazaki","year":"2000","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1007\/s00018-012-1026-1","article-title":"Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries","volume":"69","author":"Sandu","year":"2012","journal-title":"Cell. Mol. Life. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1126\/science.289.5488.2344","article-title":"Resetting of circadian time in peripheral tissues by glucocorticoid signaling","volume":"289","author":"Balsalobre","year":"2000","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Salazar, A., and von Hagen, J. (2023). Circadian oscillations in skin and their interconnection with the cycle of life. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065635"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11758","DOI":"10.1073\/pnas.1209592109","article-title":"Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis","volume":"109","author":"Geyfman","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/exd.14649","article-title":"Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management","volume":"31","author":"Paus","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/pde.13364","article-title":"Circadian rhythm in atopic dermatitis-pathophysiology and implications for chronotherapy","volume":"35","author":"Vaughn","year":"2018","journal-title":"Pediatr. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3892\/or.2022.8315","article-title":"Blue light irradiation inhibits the growth of colon cancer and activation of cancer-associated fibroblasts","volume":"47","author":"Yoshimoto","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Magni, G., Banchelli, M., Cherchi, F., Coppi, E., Fraccalvieri, M., Rossi, M., Tatini, F., Pugliese, A.M., Degl\u2019Innocenti, D.R., and Alfieri, D. (2020). Experimental study on blue light interaction with human keloid-derived fibroblasts. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120573"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/exd.12353","article-title":"Blue light inhibits transforming growth factor-1-induced myofibroblast differentiation of human dermal fibroblasts","volume":"23","author":"Taflinski","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Krassovka, J.M., Suschek, C.V., Prost, M., Grotheer, V., Schiefer, J.L., Demir, E., Fuchs, P.C., Windolf, J., St\u00fcrmer, E.K., and Opl\u00e4nder, C. (2020). The impact of non-toxic blue light (453nm) on cellular antioxidative capacity, TGF-\u03b21 signaling, and myofibrogenesis of human skin fibroblasts. J. Photochem. Photobiol. B, 209.","DOI":"10.1016\/j.jphotobiol.2020.111952"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jphotobiol.2011.02.018","article-title":"Effects of blue light irradiation on human dermal fibroblasts","volume":"103","author":"Hidding","year":"2011","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jphotobiol.2016.04.007","article-title":"Blue light does not impair wound healing in vitro","volume":"160","author":"Bumah","year":"2016","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.abd.2020.05.016","article-title":"Expression of OPN3 in fibroblasts, melanocytes, and keratinocytes of skin with facial melasma in comparison with unaffected adjacent skin","volume":"96","author":"Miot","year":"2021","journal-title":"An. Bras. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yu, L., Ren, L., and Dong, L. (2022). BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro. BMC Cardiovasc. Disord., 22.","DOI":"10.1186\/s12872-022-02822-3"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12931-016-0320-0","article-title":"Regulation of transforming growth factor-beta1 (TGF-\u03b21)-induced pro-fibrotic activities by circadian clock gene BMAL1","volume":"17","author":"Dong","year":"2016","journal-title":"Respir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41401-021-00658-9","article-title":"Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1\/\u03b1-KG-mediated glycolysis","volume":"43","author":"Xu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_47","first-page":"305","article-title":"Direct and indirect effects of blue light exposure on skin: A review of published literature","volume":"35","author":"Suitthimeatheforn","year":"2022","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jaad.2019.12.047","article-title":"Short-term exposure to blue light emitted by electronic devices does not worsen melasma","volume":"83","author":"Duteil","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1007\/s10103-021-03250-z","article-title":"The viability of human cells irradiated with 470-nm light at various radiant energies in vitro","volume":"36","author":"Bumah","year":"2021","journal-title":"Lasers Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s10103-017-2317-4","article-title":"Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods","volume":"32","author":"Ash","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1002\/lsm.20955","article-title":"Estimation of the optimal wavelengths for laser-induced wound healing","volume":"42","author":"Ankri","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1067-1927.2005.130102.x","article-title":"Tissue repair, contraction, and the myofibroblast","volume":"13","author":"Chaponnier","year":"2005","journal-title":"Wound Repair Regen."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/ags3.12055","article-title":"Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin3","volume":"2","author":"Yoshimoto","year":"2018","journal-title":"Ann. Gastroenterol. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2126\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:58:04Z","timestamp":1760104684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,9]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042126"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042126","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,9]]}}}