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

Abstract

BackgroundSpecific 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.MethodspBECs 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.ResultsAt 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.ConclusionThe 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 materialThe online version of this article (10.1186/s12931-018-0851-7) contains supplementary material, which is available to authorized users.

Consensus transcriptional regulatory networks of coronavirus-infected human cells

“…7a). Consistent with previous reports of a potential link between EMT and IAV infection 81 , we observed significant intersection between the EMT signature and the IAV HCTs (q = 1e-04).…”

“…Although EMT has been associated with infection by transmissible gastroenteritis virus 82 and IAV 81 , this is to our knowledge the first evidence connecting CoV infection, and specifically SARS2 infection, to an EMT signature. Interestingly, lipotoxin A4 has been shown to attenuate lipopolysaccharide-induced lung injury by reducing EMT 83 .…”

CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

“…Cancer stem cells characterized by high cell surface CD147 expression produce more hyaluronan, resulting in stabilization of lipid rafts, as well as reveal enhanced MMP and ABC drug transporter expression, resistance and survival [15]. Recent studies have shown that patients with severe asthma have high levels of MMP-9 in sputum [16], and influenza A virus infection increases CD147 expression in cells from asthmatics [17]. In addition, another study showed that CD147 expression is induced by high glucose (25 mM) concentration in monocytes [18].…”

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

“…IFV infection is also shown to increase miR-125a and b, and miR-132 in COPD epithelium which inhibits A20 and MAVS; and p300 and IRF3, respectively, resulting in increased susceptibility to viral infections (Hsu et al, 2016(Hsu et al, , 2017. Conversely, miR-22 was shown to be suppressed in asthmatic epithelium in IFV infection which lead to aberrant epithelial response, contributing to exacerbations (Moheimani et al, 2018). Other than these direct evidence of miRNA changes in contributing to exacerbations, an increased number of miRNAs and other non-coding RNAs responsible for immune modulation are found to be altered following viral infections (Globinska et al, 2014;Feng et al, 2018;Hasegawa et al, 2018).…”