Dataset Information

MicroRNA-27b shuttled by mesenchymal stem cell-derived exosomes prevents sepsis by targeting JMJD3 and downregulating NF-?B signaling pathway.

ABSTRACT:

Background

Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) have been shown to play roles in the pathophysiological processes of sepsis. Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to investigate the potential role and downstream molecular mechanism of exosomal miR-27b in sepsis.

Methods

Inflammation was induced in bone marrow-derived macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by cecal ligation and puncture (CLP). The expression pattern of miR-27b in MSC-derived exosomes was characterized using RT-qPCR, and its downstream gene was predicted by in silico analysis. The binding affinity between miR-27b, Jumonji D3 (JMJD3), or nuclear factor ?B (NF-?B) was characterized to identify the underlying mechanism. We induced miR-27b overexpression or downregulation, along with silencing of JMJD3 or NF-?B to examine their effects on sepsis. The production of pro-inflammatory cytokines TNF-?, IL-1?, and IL-6 was detected by ELISA.

Results

miR-27b was highly expressed in MSC-derived exosomes. Mechanistic investigations showed that miR-27b targeted JMJD3. miR-27b decreased expression of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-?B at gene promoter region. Through this, MSC-derived exosomal miR-27b diminished production of pro-inflammatory cytokines in LPS-treated BMDMs and septic mice, which could be rescued by upregulation of JMJD3 and NF-?B. Besides, in vitro findings were reproduced by in vivo findings.

Conclusion

These data demonstrated that exosomal miR-27b derived from MSCs inhibited the development of sepsis by downregulating JMJD3 and inactivating the NF-?B signaling pathway.

SUBMITTER: Sun J

PROVIDER: S-EPMC7791667 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

microRNA-27b shuttled by mesenchymal stem cell-derived exosomes prevents sepsis by targeting JMJD3 and downregulating NF-κB signaling pathway.

Sun Jia J Sun Xuan X Chen Junhui J Liao Xin X He Yixuan Y Wang Jinsong J Chen Rui R Hu Sean S Qiu Chen C

Stem cell research & therapy 20210107 1

<h4>Background</h4>Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) have been shown to play roles in the pathophysiological processes of sepsis. Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to investigate the potential role and downstream molecular mechanism of exosomal miR-27b in sepsis.<h4>Methods</h4>Inflammation was induced in bone marrow-derived macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by cecal ligation ...[more]

PMID: 33413595

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