Exosomes derived from bone marrow mesenchymal stem cells regulate pyroptosis via the miR-143-3p/myeloid differentiation factor 88 axis to ameliorate intestinal ischemia-reperfusion injury

ABSTRACT

Intestinal ischemia-reperfusion (I/R) injury is a condition in which tissue injury is aggravated after ischemia due to recovery of blood supply. Bone marrow mesenchymal stem cell-derived exosome (BMSC-exo) showed a protective effect on I/R injury. This study aimed to investigate the possible mechanisms by which BMSC-exos ameliorate intestinal I/R injury. We isolated mouse BMSC-exos by super-centrifugation and found that they effectively increased cell viability in a cell model, alleviated intestinal barrier injury in a mouse model, and downregulated the expression of inflammatory cytokines and pyroptosis-related proteins, suggesting that BMSC-exos may alleviate intestinal I/R injury in vitro and in vivo by regulating pyroptosis. We identified miR-143-3p as a differentially expressed miRNA by microarray sequencing. Bioinformatic analysis predicted a binding site between miR-143-3p and myeloid differentiation factor 88 (MyD88); a dual-luciferase reporter assay confirmed that miR-143-3p could directly regulate the expression of MyD88. Our findings suggest that miR-143-3p regulates pyroptosis by regulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) through the toll-like receptor (TLR)-4/MyD88/nuclear factor kappa-B (NF-кB) pathway. This study describes a potential strategy for the treatment of intestinal I/R injury using BMSC-exos that act by regulating pyroptosis through the miR-143-3p mediated TLR4/MyD88/NF-кB pathway.

GRAPHICAL ABSTRACT

HIGHLIGHTS

• BMSC-exos ameliorate intestinal ischemia/reperfusion (I/R) injury

• miR-143-3p levels were reduced in I/R injury and increased with BMSC-exo treatment

• miR-143-3p directly targeted and downregulated the expression of MyD88

• BMSC-exos regulate pyroptosis in intestinal I/R injury via the miR-143-3p-MyD88 axis

Keywords:

• Bone marrow mesenchymal stem cell
• exosome
• pyroptosis; intestinal ischemia-reperfusion injury
• miRNA
• MyD88/NF-кB/NLRP3 pathway

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

All authors contributed to the study conception and design. WZH and ZGR conceived and designed the research. WZH and ZGR performed most of the experiments. ZY, LJP and GWW performed parts of the experiments. WZH and YY analyzed the data. WZH, ZGR and LYF wrote the manuscript. All authors agree to be held accountable for all aspects of the research and confirm that the data are accurate. All authors reviewed and approved the manuscript.

Data availability statement

The datasets used in this study are available upon reasonable request to the corresponding author.

Ethics approval

All experimental protocols of the present study were approved by the First Hospital of Lanzhou University (No. LDYYLL2022–27) and all efforts were made to minimize animal suffering and reduce the number of animals used.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21655979.2023.2253414

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant 81960345; the Natural Science Foundation of Gansu Province under Grant 21JR11RA097; and the Foundation of the First Hospital of Lanzhou University under Grant ldyyyn2020-18.