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miR ‐378a regulates...
miR ‐378a regulates keratinocyte responsiveness to interleukin‐17A in psoriasis
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- Xia, Ping (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden;Dermatology Unit Wuhan No.1 Hospital Wuhan China
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- Pasquali, Lorenzo (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden
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- Gao, Chenying (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden;Department of Pharmacology, School of Basic Medical Sciences Xi’an Jiaotong University Health Science Center Xi’an Shaanxi 710061 China
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- Srivastava, Ankit (författare)
- Karolinska Institutet,Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden;Department of Microbiology Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute Stockholm Sweden;The Program in Epithelial Biology Stanford University School of Medicine Stanford CA USA
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- Khera, Nupur (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden
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- Freisenhausen, Jan Cedric (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden
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- Luo, Longlong (författare)
- Karolinska Institutet,Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden
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- Rosén, Einar (författare)
- Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden
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- Lierop, Anke (författare)
- Department of Dermatology University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf Germany
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- Homey, Bernhard (författare)
- Department of Dermatology University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf Germany
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- Pivarcsi, Andor (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden
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- Sonkoly, Enikö (författare)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper,Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden,Sonkoly
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Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden;Dermatology Unit Wuhan No1 Hospital Wuhan China Dermatology and Venereology Division, Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Center for Molecular Medicine (CMM) Karolinska University Hospital Stockholm Sweden (creator_code:org_t)
- 2022-05-25
- 2022
- Engelska.
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Ingår i: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 187:2, s. 211-222
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Abstract
Ämnesord
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- Background Psoriasis is an immune-mediated inflammatory skin disease, in which an interplay between infiltrating immune cells and keratinocytes sustains chronic skin inflammation. Interleukin (IL)-17A is a key inflammatory cytokine in psoriasis and its main cellular targets are keratinocytes.Objectives To explore the role of miR-378a in psoriasis.Methods Keratinocytes obtained from psoriatic skin and healthy epidermis were separated by magnetic sorting, and the expression of miR-378a was analysed by quantitative polymerase chain reaction. The regulation and function of miR-378a was studied using primary human keratinocytes. The expression of miR-378a was modulated by synthetic mimics, and nuclear factor kappa B (NF-κB) activity and transcriptomic changes were studied. Synthetic miR-378a was delivered to mouse skin in conjunction with induction of psoriasiform skin inflammation by imiquimod.Results We show that miR-378a is induced by IL-17A in keratinocytes through NF-κB, C/EBP-β and IκBζ and that it is overexpressed in psoriatic epidermis. In cultured keratinocytes, ectopic expression of miR-378a resulted in the nuclear translocation of p65 and enhanced NF-κB-driven promoter activity even in the absence of inflammatory stimuli. Moreover, miR-378a potentiated the effect of IL-17A on NF-κB nuclear translocation and downstream activation of the NF-κB pathway. Finally, injection of miR-378a into mouse skin augmented psoriasis-like skin inflammation with increased epidermal proliferation and induction of inflammatory mediators. Mechanistically, miR-378a acts as a suppressor of NFKBIA/IκBζ, an important negative regulator of the NF-κB pathway in keratinocytes.Conclusions Collectively, our findings identify miR-378a as an amplifier of IL-17A-induced NF-κB signalling in keratinocytes and suggest that increased miR-378a levels contribute to the amplification of IL-17A-driven skin inflammation in psoriasis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
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Xia, Ping
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Pasquali, Lorenz ...
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Gao, Chenying
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Srivastava, Anki ...
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Khera, Nupur
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Freisenhausen, J ...
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visa fler...
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Luo, Longlong
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Rosén, Einar
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Lierop, Anke
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Homey, Bernhard
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Pivarcsi, Andor
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Sonkoly, Enikö
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Uppsala universitet
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Karolinska Institutet