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miR-122 promotes virus-induced lung disease by targeting SOCS1
- Source :
- JCI Insight, JCI Insight, Vol 6, Iss 7 (2021)
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro–validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.
- Subjects :
- Lung Diseases
Male
0301 basic medicine
Rhinovirus
Molecular biology
Chemokine CXCL1
Chemokine CXCL2
Inflammation
Virus Replication
03 medical and health sciences
Suppressor of Cytokine Signaling 1 Protein
0302 clinical medicine
In vivo
Nasopharynx
Virology
MiR-122
Animals
Humans
Medicine
Gene silencing
Treatment Failure
Bronchitis
Asthma
Mice, Inbred BALB C
Picornaviridae Infections
Lung
business.industry
Suppressor of cytokine signaling 1
Antagomirs
Infant
General Medicine
medicine.disease
respiratory tract diseases
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Bronchiolitis
030220 oncology & carcinogenesis
Immunology
Female
medicine.symptom
business
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- JCI Insight, JCI Insight, Vol 6, Iss 7 (2021)
- Accession number :
- edsair.doi.dedup.....047e6ce8873f842d2779e1546a1a1be0