miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis
| Autor: | Richard C. Trembath, H. Hermann, Alar Aab, Michael Weichenthal, Kristi Abram, Ana Rebane, Lam C. Tsoi, Mark Boldin, Beate Rückert, Ele Prans, Paulina Wawrzyniak, Egon Urgard, Ulrich Mrowietz, Jonathan Barker, Toomas Runnel, Liisi Šahmatova, Julia Maslovskaja, James T. Elder, Eric R. Tkaczyk, Uku Haljasorg, Kai Kisand, Cezmi A. Akdis, Pärt Peterson, Maire Karelson, Nathaniel Magilnick, Elke Rodriguez, Külli Kingo, Hansjörg Baurecht, Paula Reemann, Christian Gieger, Bret Kaldvee, Stephan Weidinger, Andre Franke |
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| Rok vydání: | 2017 |
| Předmět: |
Keratinocytes
0301 basic medicine Apoptosis Dermatitis Inflammation Human skin Dermatology Biology Real-Time Polymerase Chain Reaction Biochemistry Article Proinflammatory cytokine Mice 03 medical and health sciences Psoriasis medicine Animals Humans Molecular Biology Cells Cultured Cell Proliferation Regulation of gene expression IRAK1 Cell Biology Transfection medicine.disease Molecular biology Mice Inbred C57BL Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Case-Control Studies medicine.symptom Keratinocyte |
| Zdroj: | Hermann, H, Runnel, T, Aab, A, Baurecht, H, Rodriguez, E, Magilnick, N, Urgard, E, Šahmatova, L, Prans, E, Maslovskaja, J, Abram, K, Karelson, M, Kaldvee, B, Reemann, P, Haljasorg, U, Rückert, B, Wawrzyniak, P, Weichenthal, M, Mrowietz, U, Franke, A, Gieger, C, Barker, J, Trembath, R, Tsoi, L C, Elder, J T, Tkaczyk, E R, Kisand, K, Peterson, P, Kingo, K, Boldin, M, Weidinger, S, Akdis, C A & Rebane, A 2017, ' miR-146b probably assists miRNA-146a in the suppression of keratinocyte proliferation and inflammatory responses in psoriasis ', Journal of Investigative Dermatology . https://doi.org/10.1016/j.jid.2017.05.012 J. Invest. Dermatol. 137, 1945-1954 (2017) |
| ISSN: | 0022-202X |
| Popis: | miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In this study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in the lesional skin of patients with psoriasis. The expression of miR-146a was approximately twofold higher than that of miR-146b in healthy human skin, and it was more strongly induced by stimulation of proinflammatory cytokines in keratinocytes and fibroblasts. miR-146a/b target genes regulating inflammatory responses or proliferation were altered in the skin of patients with psoriasis, among which FERMT1 was verified as a direct target of miR-146a. In silico analysis of genome-wide data from >4,000 psoriasis cases and >8,000 controls confirmed a moderate association between psoriasis and genetic variants in the miR-146a encoding gene. Transfection of miR-146a/b suppressed and inhibition enhanced keratinocyte proliferation and the expression of psoriasis-related target genes. Enhanced expression of miR-146a/b-influenced genes was detected in cultured keratinocytes from miR-146a−/− and skin fibroblasts from miR-146a−/− and miR-146b−/− mice stimulated with psoriasis-associated cytokines as compared with wild-type mice. Our results indicate that besides miR-146a, miR-146b is expressed and might be capable of modulation of inflammatory responses and keratinocyte proliferation in psoriatic skin. |
| Databáze: | OpenAIRE |
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