Journal
RESPIRATORY RESEARCH
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12931-020-01578-8
Keywords
Acute lung injury; Lipopolysaccharide; Metastasis-associated lung adenocarcinoma transcript-1; miRNA-181a-5p; Factor associated suicide; Pro-inflammatory factor
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81801936]
- Technology Commission of Shanghai Municipality [17411968500]
- Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai [PWZxq2017-05]
- Top-level Clinical Discipline Project of Shanghai Pudong [PWYgf2018-02]
- Beijing United Heart Foundation [BJUHFCSOARF201901-11]
Ask authors/readers for more resources
In patients with ALI/ARDS, MALAT1 is upregulated while miR-181a-5p is downregulated. miR-181a-5p exerts therapeutic effects by inhibiting Fas and cell apoptosis, while MALAT1 negatively regulates miR-181a-5p. Both MALAT1 antagonism and miR-181a-5p could be potential therapeutic strategies for ALI/ARDS.
Background: ALI/ARDS is a severe lung injury leading to refractory respiratory failure, accounting for high morbidity and mortality. However, therapeutic approaches are rather limited. Targeting long non-coding RNA MALAT1 and microRNA miR-181a-5p might be potential option for ALI/ARDS intervention. Objective: We aimed to investigate the role of MALAT and miR-181a-5p in the pathogenesis of ALI/ARDS, and test the therapeutic effects of targeting MALAT and miR-181a-5p for ALI/ARDS intervention in vitro. Methods: MALAT1 and miR-181a-5p levels were measured in plasma from ALI/ARDS patients. In vitro human pulmonary microvascular endothelial cell (HPMEC) injury was induced by LPS treatment, and molecular targets of MALAT1 and miR-181a-5p were explored by molecular biology approaches, mainly focusing on cell apoptosis and vascular inflammation. Interaction between MALAT1 and miR-181a-5p was also detected. Finally, the effects of targeting MALAT1 and miR-181a-5p for ALI/ARDS intervention were validated in a rat ALI/ARDS model. Results: MALAT1 upregulation and miR-181a-5p downregulation were observed in ALI/ARDS patients. Transfection of mimic miR-181a-5p into HPMECs revealed decreased Fas and apoptosis, along with reduced inflammatory factors. Fas was proved to be a direct target of miR-181a-5p. Similar effects were also present upon MALAT1 knockdown. As for the interaction between MALAT1 and miR-181a-5p, MALAT1 knockdown increased miR-181a-5p expression. Knocking down of MALAT1 and miR-181a-5p could both improve the outcome in ALI/ARDS rats. Conclusion: MALAT1 antagonism or miR-181a-5p could both be potential therapeutic strategies for ALI/ARDS. Mechanistically, miR-181a-5p directly inhibits Fas and apoptosis, along with reduced inflammation. MALAT1 negatively regulates miR-181a-5p.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available