{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:22:46Z","timestamp":1793146966707,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA\u2013miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1\u03b2 and INF\u03b3 synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.<\/jats:p>","DOI":"10.3390\/ijms21239288","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T12:24:39Z","timestamp":1607343879000},"page":"9288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-7580","authenticated-orcid":false,"given":"Lucian","family":"Beer","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Kalinina","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"K\u00f6cher","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Laggner","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Jeitler","sequence":"additional","affiliation":[{"name":"Core Facility Genomics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-3682","authenticated-orcid":false,"given":"Salman","family":"Abbas Zadeh","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Copic","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Tschachler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-925X","authenticated-orcid":false,"given":"Michael","family":"Mildner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nrg758","article-title":"Getting under the skin of epidermal morphogenesis","volume":"3","author":"Fuchs","year":"2002","journal-title":"Nat. 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