CircSLCO3A1 depletion ameliorates lipopolysaccharide-induced inflammation and apoptosis of human pulmonary alveolar epithelial cells through the miR-424-5p/HMGB3 pathway.

Background

Recent studies have shown the pathogenesis of acute lung injury (ALI) involves circular RNA (circRNA). However, there are no data on the role of circSLCO3A1 in ALI and the underlying mechanism.

Objective

ALI-like cell injury was induced by stimulating human pulmonary alveolar epithelial cells (HPAEpiCs) using lipopolysaccharide (LPS). The expression of circSLCO3A1, miR-424-5p and high mobility group box 3 (HMGB3) was detected by quantitative real-time polymerase chain reaction. Cell viability and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Enzyme-linked immunosorbent assay was performed to determine the production of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein 1 (MCP-1). Caspase-3 activity was detected by caspase-3 activity assay. Protein expression of inducible NOS (iNOS), cyclooxygenase-2 (COX2), p-p65 and p65 was analyzed by Western blot. The interactions among circSLCO3A1, miR-424-5p and HMGB3 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay.

Results

CircSLCO3A1 and HMGB3 expression were significantly increased, while miR-424-5p was decreased in LPS-treated HPAEpiCs and the serum of septic ALI patients in comparison with controls. CircSLCO3A1 knockdown assuaged LPS-induced HPAEpiC inflammation and apoptosis. Besides, circSLCO3A1 targeted miR-424-5p and regulated LPS-triggered HPAEpiC inflammation and apoptosis by binding to miR-424-5p. Under the treatment of LPS, miR-424-5p mediated HPAEpiC disorders by targeting HMGB3. Importantly, circSLCO3A1 modulated HMGB3 production by interacting with miR-424-5p.

Conclusion

CircSLCO3A1 absence assuaged LPS-induced HPAEpiC inflammation and apoptosis through the miR-424-5p/HMGB3 axis.

Highlights

CircSLCO3A1 expression was upregulated in LPS-induced HPAEpiCs and sepsis-induced ALI patients.CircSLCO3A1 depletion protected against LPS-induced HPAEpiC disorders.CircSLCO3A1 bound to miR-424-5p in HPAEpiCs.MiR-424-5p targeted HMGB3 in HPAEpiCs.CircSLCO3A1 regulated HMGB3 expression through miR-424-5p.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13273-023-00341-6.

Informations de copyright

© The Author(s) under exclusive licence to The Korean Society of Toxicogenomics and Toxicoproteomics 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Déclaration de conflit d'intérêts

Conflict of interestAuthor Yan Li declares that he has no conflict of interest. Author Chunmei Zhang declares that he has no conflict of interest. Author Zhongyan Zhao declares that he has no conflict of interest.