tetano
Editor, Senior Moderator
Respir Res. 2018 Aug 2;19(1):145. doi: 10.1186/s12931-018-0851-7.
[h=1]Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics.[/h] Moheimani F[SUP]1,[/SUP][SUP]2[/SUP], Koops J[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Williams T[SUP]3,[/SUP][SUP]4,[/SUP][SUP]6[/SUP], Reid AT[SUP]3,[/SUP][SUP]4[/SUP], Hansbro PM[SUP]3,[/SUP][SUP]4[/SUP], Wark PA[SUP]3,[/SUP][SUP]4,[/SUP][SUP]7[/SUP], Knight DA[SUP]3,[/SUP][SUP]4,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSION:[/h] 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.
[h=4]KEYWORDS:[/h] Airway remodeling; Epithelial cells; Influenza A virus; Severe asthma; microRNA
PMID: 30068332 DOI: 10.1186/s12931-018-0851-7
[h=1]Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics.[/h] Moheimani F[SUP]1,[/SUP][SUP]2[/SUP], Koops J[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Williams T[SUP]3,[/SUP][SUP]4,[/SUP][SUP]6[/SUP], Reid AT[SUP]3,[/SUP][SUP]4[/SUP], Hansbro PM[SUP]3,[/SUP][SUP]4[/SUP], Wark PA[SUP]3,[/SUP][SUP]4,[/SUP][SUP]7[/SUP], Knight DA[SUP]3,[/SUP][SUP]4,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSION:[/h] 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.
[h=4]KEYWORDS:[/h] Airway remodeling; Epithelial cells; Influenza A virus; Severe asthma; microRNA
PMID: 30068332 DOI: 10.1186/s12931-018-0851-7