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The Long Noncoding ...
The Long Noncoding RNA LINC00958 Is Induced in Psoriasis Epidermis and Modulates Epidermal Proliferation
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- Luo, Longlong (författare)
- Karolinska Institutet,Uppsala universitet,Dermatologi och venereologi,Karolinska Inst, Dept Med, Dermatol & Venereol Div, Solna, Sweden; Karolinska Univ Hosp, Ctr Mol Med, Solna, Sweden
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- Pasquali, Lorenzo (författare)
- Karolinska Inst, Dept Med, Dermatol & Venereol Div, Solna, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, Solna, Sweden.
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- Srivastava, Ankit (författare)
- Karolinska Institutet
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- Freisenhausen, Jan C. (författare)
- Uppsala universitet,Dermatologi och venereologi,Karolinska Inst, Dept Med, Dermatol & Venereol Div, Solna, Sweden; Karolinska Univ Hosp, Ctr Mol Med, Solna, Sweden
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- Pivarcsi, Andor (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Dept Med, Dermatol & Venereol Div, Solna, Sweden; Karolinska Univ Hosp, Ctr Mol Med, Solna, Sweden
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- Sonkoly, Enikö (författare)
- Karolinska Institutet,Uppsala universitet,Dermatologi och venereologi,Karolinska Inst, Dept Med, Dermatol & Venereol Div, Solna, Sweden; Karolinska Univ Hosp, Ctr Mol Med, Solna, Sweden
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 143:6, s. 999-1010
- Relaterad länk:
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Psoriasis is a common, immune-mediated skin disease characterized by epidermal hyperproliferation and chronic skin inflammation. Long noncoding RNAs are >200 nucleotide-long transcripts that possess important regulatory functions. To date, little is known about the contribution of long noncoding RNAs to psoriasis. In this study, we identify LINC00958 as a long noncoding RNA overexpressed in keratinocytes (KCs) from psoriasis skin lesions, in a transcriptomic screen performed on KCs sorted from psoriasis and healthy skin. Increased levels of LINC00958 in psoriasis KCs were confirmed by RT-qPCR and single-molecule in situ hybridization. Confocal microscopy and analysis of subcellular fractions showed that LINC00958 is mainly localized in the cytoplasm of KCs. IL-17A, a key psoriasis cytokine, induced LINC00958 in KCs through C/EBP-β and the p38 pathway. The inhibition of LINC00958 led to decreased proliferation as measured by Ki-67 expression, live cell analysis imaging, and 5-ethynyl-2-deoxyuridine assays. Transcriptomic analysis of LINC00958-depleted KCs revealed enrichment of proliferation- and cell cycle‒related genes among differentially expressed transcripts. Moreover, LINC00958 depletion led to decreased basal and IL-17A‒induced phosphorylation of p38. Furthermore, IL-17A‒induced KC proliferation was counteracted by the inhibition of LINC00958. In summary, our data support a role for the IL-17A‒induced long noncoding RNA, LINC00958, in the pathological circuits of psoriasis by reinforcing IL-17A‒induced epidermal hyperproliferation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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