{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T04:09:01Z","timestamp":1748750941016,"version":"3.41.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T00:00:00Z","timestamp":1446076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Deutsche Derma Gesell"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>Matriptase\u20101 participates in terminal keratinocyte (KC) differentiation. Knockdown of matriptase\u20101 in skin equivalent cultures leads to impaired KC differentiation and retention of nuclei in the stratum corneum. Here, we investigated the expression and regulation of matriptase\u20101 in psoriatic skin and in KC in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>Matriptase\u20101 expression in healthy and psoriatic skin and its regulation in skin equivalents were analyzed by Western blotting, immunofluorescence staining, qRT\u2010PCR, and activity assays. Involvement of the nuclear factor kappa B (NF\u03baB) signaling pathway was investigated by adenoviral overexpression of a dominant\u2010negative form of IKK2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Matriptase\u20101 expression was detected in the stratum granulosum of healthy human skin and in skin equivalent cultures. Its expression and activity was strongly reduced in lesional skin of patients with psoriasis. Addition of TNF\u03b1 to skin equivalent cultures resulted in complete loss of matriptase\u20101 expression accompanied by disturbed KC differentiation. Mechanistically, we were able to show that TNF\u03b1\u2010induced downregulation of matriptase\u20101 was inhibited by blocking the IKK2\/NF\u03baB signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Given that matriptase\u20101 participates in terminal KC differentiation, its absence in psoriatic skin lesions indicates that this contributes to the barrier disturbances in this disease. Our data suggests that blocking the IKK2\/NF\u03baB\u2010pathway represents a potential target for the treatment of psoriasis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ddg.12812","type":"journal-article","created":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T16:58:12Z","timestamp":1446137892000},"page":"1165-1174","source":"Crossref","is-referenced-by-count":1,"title":["Matriptase\u20101 expression is lost in psoriatic skin lesions and is downregulated by TNF\u03b1 in vitro"],"prefix":"10.1111","volume":"13","author":[{"given":"Michael","family":"Mildner","sequence":"first","affiliation":[{"name":"Department of Dermatology Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"Mlitz","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Ballaun","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Tschachler","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,29]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"MildnerM.A human organotypic knock\u2010down skin model to study molecules involved in epidermal keratinocyte differentiation. An alternative to knock\u2010out animal experiments in dermatological research. 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