miR155 promotes an inflammatory response in HaCaT cells via the IRF2BP2/KLF2/NFκB pathway in psoriasis.
Int J Mol Med
; 54(5)2024 11.
Article
in En
| MEDLINE
| ID: mdl-39219281
ABSTRACT
Psoriasis is a chronic inflammatory skin condition with numerous causes, including genetic, immunological and infectious factors. The course of psoriasis is long and recurrence is common; pathogenesis is not completely understood. However, there is an association between advancement of psoriasis and aberrant microRNA (miR or miRNA)155 expression. Through bioinformatics, the present study aimed to analyze the differentially expressed genes and miRNAs in psoriasis and its biological mechanism and function psoriatic inflammation. First of all, differentially expressed genes (DEGs) and miRNAs (DEMs) in patients with psoriasis were identified using GEO2R interactive web application. A psoriasis inflammatory model was established using lipopolysaccharide (LPS)treated HaCaT keratinocytes, which were transfected with miR155 mimic or inhibitor. Cell Counting Kit8 was used for the assessment of cell viability and proliferation, and changes in the cell cycle were examined using flow cytometry. ELISA and reverse transcriptionquantitative PCR (RTqPCR) were used to detect the expression levels of the inflammatory factors IL1ß and IL6. The dualluciferase reporter assay was used to verify the targeting association between miR1555p and IFN regulatory factor 2 binding protein 2 (IRF2BP2). To verify the targeting association of miR155 and the IRF2BP2/kruppellike factor 2 (KLF2)/NFκB signaling pathway, expression levels of IRF2BP2, KLF2 and p65 were identified by RTqPCR and western blotting. IRF2BP2 levels were also confirmed by immunofluorescence, in conjunction with bioinformatics database analysis. Overexpression of miR155 inhibited proliferation of HaCaT cells and increased the number of cells in S phase and decreasing number of cells in G1 and G2 phase. In the LPSinduced inflammatory state, miR155 overexpression heightened the inflammatory response of HaCaT cells while inhibition of miR155 lessened it. Suppression of inflammatory cytokine expression by miR1555p inhibitor was reversed by knockdown of IRF2BP2. miR155 was shown to interact with IRF2BP2 to negatively regulate its expression, leading to decreased KLF2 expression and increased p65 expression and secretion of inflammatory factors, intensifying the inflammatory response of HaCaT cells. Therefore, miR155 may contribute to development of psoriasis by inducing tissue and cell damage by increasing the inflammatory response of HaCaT cells via the IRF2BP2/KLF2/NFκB pathway. In conclusion, the results of the present study offer novel perspectives on the role of miR155 in the onset and progression of psoriasis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Psoriasis
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Signal Transduction
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NF-kappa B
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MicroRNAs
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Kruppel-Like Transcription Factors
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Inflammation
Limits:
Humans
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2024
Document type:
Article
Country of publication:
Greece