Bone marrow mesenchymal stem cell-derived exosomes miR-202-5p inhibited pyroptosis to alleviate lung ischemic-reperfusion injury by targeting CMPK2
Zhi-Lu Sun1, Ting You1, Bi-Hong Zhang1
1The First Affiliated Hospital, Emergency Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan Province, People's Republic of China.
Abstract:
Bone mesenchymal stem cell-derived exosome (BMSC-exosome) is a potential candidate for lung ischemia-reperfusion injury (LIRI) treatment. This study aims to investigate the anti-pyroptosis effect of BMSC-exosomes in LIRI. The LIRI cell model was established by hypoxia/reoxygenation (H/R) treatment. Interleukin (IL)-1β and IL-18 levels were examined by enzyme-linked immunosorbent assay. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Lactate dehydrogenase (LDH) release was examined using a LDH assay kit. The interaction between microRNA (miR)-202-5p and cytidine monophosphate kinase 2 (CMPK2) was analyzed using dual-luciferase reporter assay and RNA immunoprecipitation. BMSC-exosomes promoted cell viability and suppressed pyroptosis in H/R-treated mouse lung epithelial. miR-202-5p was enriched in BMSC-exosomes, and exosomal miR-202-5p inhibition upregulated pyroptosis-associated proteins, including cleaved N-terminal Gasdermin D, nucleotide-binding domain-like receptor family member pyrin domain-containing protein 3, and Caspase1. Meanwhile, miR-202-5p suppressed CMPK2 expression by directly targeting CMPK2. Expectedly, CMPK2 knockdown reversed the promoting effect of exosomal miR-202-5p inhibition on pyroptosis in LIRI. Therefore, BMSC-derived exosome miR-202-5p repressed pyroptosis to inhibit LIRI progression by targeting CMPK2.
Insights
Bone mesenchymal stem cell-derived exosomes (BMSC-exosomes) show promise in treating lung ischemia-reperfusion injury (LIRI). These exosomes, specifically miR-202-5p, inhibit pyroptosis by targeting CMPK2, thereby reducing LIRI progression.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Cell Biology
Background:
- Lung ischemia-reperfusion injury (LIRI) is a critical clinical challenge.
- Pyroptosis, a pro-inflammatory form of cell death, significantly contributes to LIRI pathogenesis.
- Mesenchymal stem cell-derived exosomes (BMSC-exosomes) are explored for therapeutic potential in LIRI.
Purpose of the Study:
- To investigate the anti-pyroptosis effect of BMSC-exosomes in a cellular model of LIRI.
- To elucidate the molecular mechanism underlying the protective action of BMSC-exosomes in LIRI.
Main Methods:
- Established a LIRI cell model using hypoxia/reoxygenation (H/R) treatment.
- Quantified inflammatory markers (IL-1β, IL-18) and cell viability (MTT assay).
- Assessed pyroptosis via lactate dehydrogenase (LDH) release and analyzed key pyroptosis-related proteins.
- Investigated the role of microRNA-202-5p (miR-202-5p) and its target cytidine monophosphate kinase 2 (CMPK2) using dual-luciferase reporter and RNA immunoprecipitation assays.
Main Results:
- BMSC-exosomes significantly promoted cell viability and suppressed pyroptosis in H/R-treated lung epithelial cells.
- miR-202-5p was enriched in BMSC-exosomes and its inhibition upregulated pyroptosis markers.
- miR-202-5p directly targeted and suppressed CMPK2 expression.
- Knockdown of CMPK2 reversed the effects of exosomal miR-202-5p inhibition on pyroptosis.
Conclusions:
- BMSC-derived exosome miR-202-5p exerts a protective effect against LIRI.
- This therapeutic effect is mediated by the repression of pyroptosis through targeting CMPK2.
- BMSC-exosomes represent a promising therapeutic strategy for LIRI treatment.
