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Updated: Aug 16, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Long noncoding RNA MALAT1 inhibition attenuates sepsis-induced acute lung injury through modulating the
Ying Li1, Wenbiao Xiao2, Xiao Lin1
1Department of Critical Care Medicine, The First Affiliated Hospital, Fujian Medical University, Fujian, Fuzhou, China.
Abstract:
This research aimed to investigate the role of the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-129-5p (miR-129-5p)/paired box gene 6 (PAX6) axis in sepsis-induced acute lung injury (ALI). MLE-12 cells and C57BL/6 mice were induced by LPS to establish lung injury in in vitro and in vivo models. Cell viability and apoptosis were measured by cell counting kit-8 assay and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Levels of inflammatory cytokines in cell supernatants and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Lung injury was evaluated by lung wet weight-to-dry weight ratio and hematoxylin-eosin staining. MALAT1, PAX6, and zinc finger E-box-binding homeobox 2 (ZEB2) expression was elevated and miR-129-5p expression was reduced in the serum of patients with sepsis-induced ALI, LPS-induced MLE-12 cells, and lung tissues of ALI mice. MALAT1 interference delayed the LPS-induced cell proliferation decrease, apoptosis increase, and inflammatory factor increase. miR-129-5p inhibition could reverse the delaying effect of MALAT1 interference on LPS-induced lung cell injury. PAX6 overexpression (oe) reversed the inhibitory effect of miR-129-5p oe on LPS-induced lung cell injury. Downregulating MALAT1 reduced pulmonary edema, inflammatory cytokine levels, lung injury, and apoptosis in ALI mice. Moreover, miR-129-5p suppression or PAX6 oe reversed the delaying effect of MALAT1 interference on sepsis-induced ALI. MALAT1 aggravates sepsis-induced ALI via the miR-129-5p/PAX6/ZEB2 axis.
Insights
The long noncoding RNA MALAT1 aggravates sepsis-induced acute lung injury (ALI) by regulating the miR-129-5p/PAX6/ZEB2 axis, impacting cell viability, apoptosis, and inflammation.
Area of Science:
- Molecular Biology
- Cell Biology
- Pathology
Background:
- Sepsis-induced acute lung injury (ALI) is a critical condition with high mortality.
- The molecular mechanisms underlying ALI pathogenesis require further elucidation.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in inflammatory diseases.
Purpose of the Study:
- To investigate the role of the MALAT1/miR-129-5p/PAX6 axis in sepsis-induced ALI.
- To elucidate the molecular mechanism by which MALAT1 influences ALI progression.
Main Methods:
- In vitro (MLE-12 cells) and in vivo (C57BL/6 mice) models of LPS-induced ALI were established.
- Cell viability, apoptosis, inflammatory cytokine levels, and lung injury were assessed.
- Expression levels of MALAT1, miR-129-5p, PAX6, and ZEB2 were analyzed.
Main Results:
- MALAT1, PAX6, and ZEB2 expression was upregulated, while miR-129-5p was downregulated in ALI.
- MALAT1 interference attenuated LPS-induced cell injury, apoptosis, and inflammation.
- miR-129-5p inhibition or PAX6 overexpression reversed the protective effects of MALAT1 interference.
- Downregulating MALAT1 reduced lung injury and inflammation in ALI mice.
Conclusions:
- MALAT1 exacerbates sepsis-induced ALI through the miR-129-5p/PAX6/ZEB2 pathway.
- Targeting the MALAT1 axis may offer a therapeutic strategy for ALI.
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