{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:38:20Z","timestamp":1790696300464,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T00:00:00Z","timestamp":1405468800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p> Netherton syndrome (<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>;<jats:styled-content style=\"fixed-case\"> OMIM<\/jats:styled-content> 256500) is a genetic skin disease resulting from defects in the serine protease inhibitor <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>azal\u2010type 5 (<jats:styled-content style=\"fixed-case\">SPINK<\/jats:styled-content>5) gene, which encodes the protease inhibitor lympho\u2010epithelial <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>azal type inhibitor (<jats:styled-content style=\"fixed-case\">LEKTI<\/jats:styled-content>). We established a <jats:styled-content style=\"fixed-case\">SPINK<\/jats:styled-content>5 knockdown skin model by transfecting <jats:styled-content style=\"fixed-case\">SPINK<\/jats:styled-content>5 small interfering <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>) into normal human epidermal keratinocytes, which were used together with fibroblast\u2010populated collagen gels to generate organotypic skin cultures. This model recapitulates some of the <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content> skin morphology: thicker, parakeratotic stratum corneum frequently detached from the underlying epidermis and loss of corneodesmosomes. As enhanced serine protease activity has been implicated in the disease pathogenesis, we investigated the impact of the kallikreins <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>5 [stratum corneum trypsin\u2010like enzyme (<jats:styled-content style=\"fixed-case\">SCTE<\/jats:styled-content>)] and <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>7 [stratum corneum chymotrypsin\u2010like enzyme (<jats:styled-content style=\"fixed-case\">SCCE<\/jats:styled-content>)] on the <jats:styled-content style=\"fixed-case\">SPINK<\/jats:styled-content>5 knockdown phenotype by generating double knockdowns in the organotypic model. Knockdown of <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>5 or <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>7 partially ameliorated the epidermal architecture: increased epidermal thickness and expression of desmocollin 1 (<jats:styled-content style=\"fixed-case\">DSC<\/jats:styled-content>1), desmoglein 1 (<jats:styled-content style=\"fixed-case\">DSG<\/jats:styled-content>1) and (pro)filaggrin. Thus, inhibition of serine proteases <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>5 and <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>7 could be therapeutically beneficial in <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/exd.12451","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T17:03:42Z","timestamp":1400691822000},"page":"524-526","source":"Crossref","is-referenced-by-count":29,"title":["<scp>SPINK<\/scp>5 knockdown in organotypic human skin culture as a model system for <scp>N<\/scp>etherton syndrome: effect of genetic inhibition of serine proteases kallikrein 5 and kallikrein 7"],"prefix":"10.1111","volume":"23","author":[{"given":"Shirley","family":"Wang","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Olt","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schoefmann","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Stuetz","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Winiski","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wolff\u2010Winiski","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,16]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1558-1"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg247"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.22512.x"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-02-0124"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.174"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1493"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700284"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41440"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.07.035"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000246431"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.1996.tb01202.x"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.417"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.23547.x"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1586\/edm.11.85"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131797"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.11.005"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200105009"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-010-0513-4"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.033969"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12451","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T07:12:58Z","timestamp":1695539578000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1111\/exd.12451"],"URL":"https:\/\/doi.org\/10.1111\/exd.12451","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7]]}}}