{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:47:57Z","timestamp":1773812877865,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mammalian wound healing is a carefully orchestrated process in which many cellular and molecular effectors respond in concert to perturbed tissue homeostasis in order to close the wound and re\u2010establish the skin barrier. The roles of many of these molecular effectors, however, are not entirely understood. Our lab previously demonstrated that the atypical sodium channel Na<jats:sub>x<\/jats:sub> (encoded by <jats:italic>Scn7a<\/jats:italic>) responds to wound\u2010induced epidermal dehydration, resulting in molecular cascades that drive pro\u2010inflammatory signaling. Acute inhibition of Na<jats:sub>x<\/jats:sub> was sufficient to attenuate dermatopathological symptoms in models of hypertrophic scar and dermatitis. To date, however, the role of Na<jats:sub>x<\/jats:sub> in excisional wound healing has not been demonstrated. Here we report development of a knockout mouse that lacks expression of functional Na<jats:sub>x<\/jats:sub>, and we demonstrate that lack of functional Na<jats:sub>x<\/jats:sub> results in deficient wound healing in a murine splinted excisional wound healing model. This deficiency in wound healing was reflected in impaired re\u2010epithelialization and decreased keratinocyte proliferation, a finding which was further supported by decreased proliferation upon Na<jats:sub>x<\/jats:sub> knockdown in HaCaT cells in vitro. Defective wound healing was observed alongside increased expression of inflammatory genes in the wound epidermis of Na<jats:sub>x<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup> mice, suggesting that mice lacking functional Na<jats:sub>x<\/jats:sub> retain the ability to undergo skin inflammation. Our observations here motivate further investigation into the roles of Na<jats:sub>x<\/jats:sub> in wound healing and other skin processes.<\/jats:p>","DOI":"10.1111\/wrr.12885","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T03:57:31Z","timestamp":1609387051000},"page":"306-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Knockout of sodium channel Na<sub>x<\/sub> delays re\u2010epithelializathion of splinted murine excisional wounds"],"prefix":"10.1111","volume":"29","author":[{"given":"Chun","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Department of Plastic and Cosmetic Surgery First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-4294","authenticated-orcid":false,"given":"David","family":"Dolivo","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-6244","authenticated-orcid":false,"given":"Yingxing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Combat Wound Repair US Army Institute of Surgical Research, JB Fort Sam Houston  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Galiano","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seok Jong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Mustoe","sequence":"additional","affiliation":[{"name":"Department of Surgery Northwestern University\u2010Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.477"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00352.2015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad0286"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13917"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-020-0371-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.270.2.C688"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2004.12404.x"},{"key":"e_1_2_8_9_1","unstructured":"RissTL MoravecRA NilesAL DuellmanS BeninkHA WorzellaTJ et al.Cell viability assays. Assay Guidance Manual [Internet]: Eli Lilly & Company and the National Center for Advancing Translational Sciences;2016."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07743.2000"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2011\/969618","article-title":"Surgical approaches to create murine models of human wound healing","volume":"2011","author":"Wong VW","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33123"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2007.00280.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103217"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2009.05.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2014.12.026"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000035024.75914.39"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2007.00225.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(89)91043-0"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400642200"},{"issue":"2","key":"e_1_2_8_22_1","first-page":"173","article-title":"Tumor necrosis factor\u2010\u03b1 inhibits in vivo collagen synthesis","volume":"113","author":"Regan MC","year":"1993","journal-title":"Surgery"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.15.5277"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","unstructured":"ZhongA XuW ZhaoJ et al.S100A8 and S100A9 are induced by decreased hydration in the epidermis and promote fibroblast activation and fibrosis in the dermis.2016;186(1):109\u2010122.","DOI":"10.1016\/j.ajpath.2015.09.005"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3641"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858414541009"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-020-02389-y"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2016.05.017"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36187"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201712-2410OC"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009337"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4MR0316-102R"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12885","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/wrr.12885","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:07:31Z","timestamp":1693192051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.12885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,30]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/wrr.12885"],"URL":"https:\/\/doi.org\/10.1111\/wrr.12885","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,30]]},"assertion":[{"value":"2020-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}