Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics

Autor: Darryl A. Knight, Fatemeh Moheimani, Jorinke Koops, Philip M. Hansbro, Teresa Williams, Peter A. B. Wark, Andrew T. Reid
Přispěvatelé: Faculteit Medische Wetenschappen/UMCG
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Severe asthma
Respiratory System
Epithelial cells
medicine.disease_cause
chemistry.chemical_compound
Influenza A Virus
H1N1 Subtype
Influenza A virus
Cells
Cultured
microRNA
PROLIFERATION
Airway remodeling
Middle Aged
3. Good health
medicine.anatomical_structure
DIFFERENTIATION
Female
Adult
RNA EXPRESSION
Respiratory Mucosa
Biology
Histone Deacetylases
03 medical and health sciences
Immune system
Influenza
Human
medicine
Humans
Antagomir
Aged
lcsh:RC705-779
Messenger RNA
MESENCHYMAL TRANSITION
Innate immune system
H1N1 INFLUENZA
Research
MIR-22
lcsh:Diseases of the respiratory system
Asthma
Epithelium
Repressor Proteins
AIRWAY EPITHELIUM
MicroRNAs
030104 developmental biology
chemistry
Immunology
CELLS
Basigin
INNATE IMMUNITY
Respiratory epithelium
INFLAMMATORY RESPONSES
Zdroj: Respiratory Research, Vol 19, Iss 1, Pp 1-16 (2018)
Respiratory Research, 19:145. BioMed Central Ltd.
Respiratory Research
ISSN: 1465-993X
DOI: 10.1186/s12931-018-0851-7
Popis: Background Specific microRNAs (miRNAs) play essential roles in airway remodeling in asthma. Infection with influenza A virus (IAV) may also magnify pre-existing airway remodeling leading to asthma exacerbation. However, these events remain to be fully defined. We investigated the expression of miRNAs with diverse functions including proliferation (miR-20a), differentiation (miR-22) or innate/adaptive immune responses (miR-132) in primary bronchial epithelial cells (pBECs) of asthmatics following infection with the H1N1 strain of IAV. Methods pBECs from subjects (n = 5) with severe asthma and non-asthmatics were cultured as submerged monolayers or at the air-liquid-interface (ALI) conditions and incubated with IAV H1N1 (MOI 5) for up to 24 h. Isolated miRNAs were subjected to Taqman miRNAs assays. We confirmed miRNA targets using a specific mimic and antagomir. Taqman mRNAs assays and immunoblotting were used to assess expression of target genes and proteins, respectively. Results At baseline, these miRNAs were expressed at the same level in pBECs of asthmatics and non-asthmatics. After 24 h of infection, miR-22 expression increased significantly which was associated with the suppression of CD147 mRNA and HDAC4 mRNA and protein expression in pBECs from non-asthmatics, cultured in ALI. In contrast, miR-22 remained unchanged while CD147 expression increased and HDAC4 remained unaffected in cells from asthmatics. IAV H1N1 mediated increases in SP1 and c-Myc transcription factors may underpin the induction of CD147 in asthmatics. Conclusion The different profile of miR-22 expression in differentiated epithelial cells from non-asthmatics may indicate a self-defense mechanism against aberrant epithelial responses through suppressing CD147 and HDAC4, which is compromised in epithelial cells of asthmatics. Electronic supplementary material The online version of this article (10.1186/s12931-018-0851-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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