{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:37:33Z","timestamp":1787589453674,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173421"],"award-info":[{"award-number":["82173421"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20Y11905700"],"award-info":[{"award-number":["20Y11905700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical innovation research special project of Shanghai Science and Technology Commission","award":["82173421"],"award-info":[{"award-number":["82173421"]}]},{"name":"Medical innovation research special project of Shanghai Science and Technology Commission","award":["20Y11905700"],"award-info":[{"award-number":["20Y11905700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Melasma is a common refractory acquired pigmentary skin disease that mainly affects middle-aged women. The pathogenesis of melasma is still uncertain, while abnormal vascular endothelial cells may play a role. We previously demonstrated the yellow light of light-emitting diodes (LED) could inhibit melanogenesis through the photobiomodulation (PBM) of melanocytes and keratinocytes. In the current study, we investigated the effect of 590 nm LED on the function of human microvascular endothelial cells (HMEC-1). We revealed 0\u201340 J\/cm2 590 nm LED had no toxic effect on HMEC-1 in vitro. 590 nm LED irradiation significantly reduced cell migration, tube formation, as well as the expression of vascular endothelial growth factor (VEGF) and stem cell factor (SCF), a pro-melanogenic factor. Moreover, we illustrated that 590 nm LED inhibited the phosphorylation of the AKT\/PI3K\/mTOR signaling pathway, and the inhibitory effect on HMEC-1 could be partially reversed by insulin-like growth factor 1 (IGF-1), an AKT\/PI3K\/mTOR pathway agonist. Besides, we conducted a pilot clinical study and observed a marked improvement on facial erythema and pigmentation in melasma patients after amber LED phototherapy. Taken together, 590 nm LED inhibited HMEC-1 migration, tube formation and the secretion of VEGF and SCF, predominantly through the inhibition of the AKT\/PI3K\/mTOR pathway, which may serve as a novel therapeutic option for melasma.<\/jats:p>","DOI":"10.3390\/cells11243949","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T04:38:54Z","timestamp":1670387934000},"page":"3949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["590 nm LED Irradiation Improved Erythema through Inhibiting Angiogenesis of Human Microvascular Endothelial Cells and Ameliorated Pigmentation in Melasma"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-6062","authenticated-orcid":false,"given":"Xiaoxi","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leihong","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-5667","authenticated-orcid":false,"given":"Chengfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/exd.13844","article-title":"Melasma: Updates and perspectives","volume":"28","author":"Kwons","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jdermsci.2007.01.009","article-title":"The vascular characteristics of melasma","volume":"46","author":"Kim","year":"2007","journal-title":"J. Dermatol.Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1038\/jid.2015.332","article-title":"Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation","volume":"135","author":"Regazzetti","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6740408","DOI":"10.1155\/2018\/6740408","article-title":"Cellular and Molecular Heterogeneity Associated with Vessel Formation Processes","volume":"2018","author":"Castro","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1038\/s41598-018-22608-y","article-title":"Ultraviolet-irradiated endothelial cells secrete stem cell factor and induce epidermal pigmentation","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/pcmr.12491","article-title":"TGFbeta1 derived from endothelial cells inhibits melanogenesis","volume":"29","author":"Park","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s10439-011-0454-7","article-title":"The nuts and bolts of low-level laser (light) therapy","volume":"40","author":"Chung","year":"2012","journal-title":"Ann. Biomed. Eng."},{"key":"ref_8","first-page":"41","article-title":"Low-level laser (light) therapy (LLLT) in skin: Stimulating, healing, restoring","volume":"32","author":"Avci","year":"2013","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"675","DOI":"10.2340\/00015555-1319","article-title":"Light-emitting diodes at 830 and 850 nm inhibit melanin synthesis in vitro","volume":"92","author":"Kim","year":"2012","journal-title":"Acta Derm.-Venereol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jdermsci.2017.10.001","article-title":"Light-emitting diode 585nm photomodulation inhibiting melanin synthesis and inducing autophagy in human melanocytes","volume":"89","author":"Chen","year":"2018","journal-title":"J. Dermatol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jdermsci.2020.03.002","article-title":"585\u2009nm light-emitting diodes inhibit melanogenesis through upregulating H19\/miR-675 axis in LEDs-irradiated keratinocytes by paracrine effect","volume":"98","author":"Jin","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103959","DOI":"10.1016\/j.mvr.2019.103959","article-title":"Low-level laser therapy induces human umbilical vascular endothelial cell proliferation, migration and tube formation through activating the PI3K\/Akt signaling pathway","volume":"129","author":"Li","year":"2020","journal-title":"Microvasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1111\/bph.15303","article-title":"Protection against light-induced retinal degeneration via dual anti-inflammatory and anti-angiogenic functions of thrombospondin-1","volume":"179","author":"Ju","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1001\/archderm.1994.01690060057005","article-title":"Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial","volume":"130","author":"Griffiths","year":"1994","journal-title":"Arch. Dermatol."},{"key":"ref_15","first-page":"e51312","article-title":"Endothelial cell tube formation assay for the in vitro study of angiogenesis","volume":"9","author":"Henry","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.7150\/thno.35219","article-title":"Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK\/ERK and PI3K\/AKT pathways via distinct mechanisms","volume":"9","author":"Su","year":"2019","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1039\/c9pp00089e","article-title":"Under the spotlight: Mechanisms of photobiomodulation concentrating on blue and green light","volume":"18","author":"Serrage","year":"2019","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jid.2017.07.833","article-title":"Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3","volume":"138","author":"Regazzetti","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jphotobiol.2017.06.014","article-title":"Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells","volume":"173","author":"Yang","year":"2017","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.23.12.120901","article-title":"Review of light parameters and photobiomodulation efficacy: Dive into complexity","volume":"23","author":"Zein","year":"2018","journal-title":"J. Biomed. Opt."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/1523-1747.ep12479191","article-title":"The optics of human skin","volume":"77","author":"Anderson","year":"1981","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","first-page":"193","article-title":"Bunsen-Roscoe law","volume":"108","author":"Bunsenr","year":"1859","journal-title":"Photochem. Stud. Ann. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/lsm.20950","article-title":"Effect of pulsing in low-level light therapy","volume":"42","author":"Hashmi","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/1011-1344(89)80088-0","article-title":"Laser biostimulation: A photobiological phenomenon","volume":"3","author":"Karu","year":"1989","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0014-5793(97)01481-6","article-title":"Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42\/p44 mitogen-activated protein kinase","volume":"420","author":"Cospedal","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/biof.29","article-title":"Physiological factors that regulate skin pigmentation","volume":"35","author":"Yamaguchi","year":"2009","journal-title":"Biofactors"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.0906-6705.2005.00345.x","article-title":"Modulation of vascular endothelial growth factor receptors in melanocytes","volume":"14","author":"Kim","year":"2005","journal-title":"Exp. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101349","DOI":"10.1016\/j.arr.2021.101349","article-title":"Epigenetic regulation of melanogenesis","volume":"69","author":"Zhou","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fnmol.2011.00051","article-title":"PI3K\/AKT\/mTOR Pathway in Angiogenesis","volume":"4","author":"Karar","year":"2011","journal-title":"Front. Mol. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4161\/cbt.2.6.678","article-title":"Mechanisms by which IGF-I may promote cancer","volume":"2","author":"Grimberg","year":"2003","journal-title":"Cancer Biol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/lsm.20412","article-title":"Blue and red light combination LED phototherapy for acne vulgaris in patients with skin phototype IV","volume":"39","author":"Lee","year":"2007","journal-title":"Lasers Surg. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1111\/j.1524-4725.2005.31926","article-title":"Clinical experience with light-emitting diode (LED) photomodulation","volume":"31","author":"Weiss","year":"2005","journal-title":"Dermatol. Surg."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/24\/3949\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:35:34Z","timestamp":1760146534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/24\/3949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":32,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cells11243949"],"URL":"https:\/\/doi.org\/10.3390\/cells11243949","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,7]]}}}