{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:04:54Z","timestamp":1773201894511,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972919"],"award-info":[{"award-number":["81972919"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Repigmentation of the skin in patients with vitiligo represents an intricate process in which the depigmented epidermis is replenished by functional melanocytes (MCs) that migrate from undamaged hair follicles and\/or surrounding areas. We characterized whether MCs release a secreted form of Pmel17 (sPmel17) protein after exposure to UVB, thereby weakening the cell\u2010cell adhesions of keratinocytes (KCs), which provides MCs the opportunity to migrate to areas devoid of MCs. At first, we examined the interactions of sPmel17 and FHL2 (four\u2010and\u2010a\u2010half LIM domain protein 2) in KCs treated with the conditioned media (CM) from MCs exposed to UVB. The results showed that both the protein and mRNA levels of FHL2 were significantly upregulated in KCs treated with sPmel17\u2010enriched CM from UVB\u2010exposed MCs. We also found that there are physical interactions between sPmel17 and FHL2 as analyzed by reciprocal coimmunoprecipitation assays and double immunofluorescence staining. The CM from UVB\u2010exposed MCs signaled KCs to remodel the actin cytoskeleton and reduce E\u2010cadherin expression. However, the CM from UVB\u2010exposed and Pmel17\u2010silenced or from UVB\u2010unexposed MCs failed to do this. To further determine the in situ distributions of sPmel17, FHL2, and E\u2010cadherin, we examined the expression profiles of those proteins in the skin from healthy subjects and from depigmented or repigmented vitiligo using immunofluorescence and immunohistochemical staining. The results showed that the expression of sPmel17 was positively correlated with FHL2 but not to E\u2010cadherin. The colocalization of FHL2 and sPmel17 was also observed in UVB\u2010exposed mouse tail skin. Together, the upregulation of FHL2 in KCs requires stimulation by sPmel17 secreted from MCs and activation of the sPmel17\u2010FHL2\u2010E\u2010cadherin axis offers a potential therapeutic target to expedite the repigmentation process in patients with vitiligo.<\/jats:p>","DOI":"10.1155\/2022\/1856830","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:05:33Z","timestamp":1644537933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["sPmel17 Secreted by Ultraviolet B\u2010Exposed Melanocytes Alters the Intercellular Adhesion of Keratinocytes"],"prefix":"10.1155","volume":"2022","author":[{"given":"Shuang-Hai","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-827X","authenticated-orcid":false,"given":"Tie-Chi","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8622-7"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12974"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/pde.13517"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000794"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2017.0002"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.126"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.045"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213729"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808904200"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.168088"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-140921"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802765RR"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.01.033"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.5807"},{"key":"e_1_2_10_15_2","article-title":"Induction of retinal-dependent calcium influx in human melanocytes by UVA or UVB radiation contributes to the stimulation of melanosome transfer","volume":"50","author":"Hu Q. M.","year":"2018","journal-title":"Cell Proliferation"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.05.009"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4478"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.6170"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.2119\/2007-00118.Joos"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13858"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.11.015"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12985"},{"key":"e_1_2_10_23_2","first-page":"219","article-title":"Protein-protein interactions of the LIM-only protein FHL2 and functional implication of the interactions relevant in cardiovascular disease","volume":"2","author":"Tran M. 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