MiR-199a-3p Attenuates Sepsis-Induced Acute Lung Injury by Targeting NLRP1 and Suppressing Caspase-1/GSDMD-Mediated Pyroptosis in a CLP Rat Model

DOI: https://doi.org/10.62517/jmhs.202505412

Author(s)

Wenhan Xia1,*, Liming Liu2, Xingmi Ye2, Huiwei He1, Cong Wang1

Affiliation(s)

1Department of Critical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China 2Ji'an County People's Hospital, Ji'an, Jiangxi, China *Corresponding Author

Abstract

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of mortality in critical care. MicroRNAs play essential roles in regulating inflammation and programmed cell death. In this study, miR-199a-3p was identified as one of the most significantly downregulated miRNAs in ALI. Bioinformatic and luciferase assays confirmed NLRP1 as its direct target. Using a cecal ligation and puncture (CLP) rat model, we found that CLP markedly decreased miR-199a-3p expression while upregulating NLRP1, cleaved Caspase-1, and GSDMD-N, leading to severe lung injury. Lentiviral overexpression of miR-199a-3p significantly reduced pulmonary inflammation, cytokine release, and histopathological damage by suppressing the NLRP1/Caspase-1/GSDMD pathway. These results demonstrate that miR-199a-3p protects against sepsis-induced ALI by inhibiting pyroptosis through direct targeting of NLRP1, suggesting its potential as a therapeutic target for ALI/ARDS.

Keywords

miR-199a-3p; NLRP1; Pyroptosis; Acute Lung Injury; Sepsis; Caspase-1; GSDMD; Cecal Ligation and Puncture (CLP)

References

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