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MSC Promotes the Secretion of Exosomal miR-34a-5p and Improve Intestinal Barrier Function Through METTL3-Mediated

Yi-Jun Li1, Qing-Wen Xu1, Cong-Hui Xu1

  • 1Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University, No.374, Dianmian Road, Kunming, 650101, Yunnan Province, People's Republic of China.

Molecular Neurobiology
|June 10, 2022
PubMed

Insights

Mesenchymal stem cells (MSCs) protect against intestinal ischemia/reperfusion injury (IIRI) by secreting exosomal miR-34a-5p. This microRNA

Area of Science:

  • Gastroenterology
  • Regenerative Medicine
  • Molecular Biology

Background:

  • Intestinal ischemia/reperfusion injury (IIRI) presents a significant clinical challenge with high mortality.
  • Mesenchymal stem cell (MSC) therapy shows promise, but the mechanisms of MSC-derived exosomes in IIRI are not fully understood.
  • Exosomal microRNAs (miRNAs) are crucial mediators, yet their role in MSC-based IIRI treatment requires investigation.

Purpose of the Study:

  • To investigate the function and regulatory mechanism of MSC-derived exosomal miRNAs in intestinal ischemia/reperfusion injury (IIRI).
  • To elucidate the role of miR-34a-5p and its regulatory pathway involving METTL3/IGF2BP3-mediated m6A modification in MSC-treated IIRI.

Main Methods:

  • Established in vitro and in vivo models of intestinal ischemia/reperfusion injury (IIRI).
  • Characterized mesenchymal stem cells (MSCs) and their derived exosomes using immunofluorescence, flow cytometry, TEM, and western blot.
  • Assessed cell viability, apoptosis, and intestinal integrity using CCK-8, TUNEL, and TER assays; analyzed molecular mechanisms via qRT-PCR, western blot, MeRIP-qPCR, RNA pull-down, and RIP assays.

Main Results:

  • MSC-derived exosomal miR-34a-5p significantly alleviated oxygen-glucose deprivation/reperfusion (OGD/R)-induced injury in vitro and in vivo.
  • MSCs ameliorated IIRI by modulating the METTL3/IGF2BP3 pathway, which mediates m6A modification of pre-miR-34A.
  • MSC treatment promoted the secretion of exosomal miR-34a-5p, enhancing intestinal barrier function.

Conclusions:

  • MSC-derived exosomal miR-34a-5p is a key therapeutic factor in mitigating intestinal ischemia/reperfusion injury.
  • The METTL3/IGF2BP3-mediated m6A modification of pre-miR-34a is a critical regulatory mechanism for exosome secretion and therapeutic efficacy.
  • This study highlights a novel therapeutic strategy utilizing MSC-derived exosomes for treating IIRI.
Keywords:
IGF2BP3METTL3MSC-derived exosomesm6A modificationmiR-34a-5p

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