Neutrophil-derived microRNAs put the (DNA) breaks on intestinal mucosal healing
Eóin N. McNamee
Eóin N. McNamee
Published January 14, 2019
Citation Information: J Clin Invest. 2019;129(2):499-502. https://doi.org/10.1172/JCI125779.
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Commentary

Neutrophil-derived microRNAs put the (DNA) breaks on intestinal mucosal healing

Abstract

A predominant feature of intestinal inflammation is the accumulation of neutrophils, which dictates a fine balance between epithelial repair or progression to chronic inflammation. While the processes of mucosal healing are well studied, how neutrophils advance an inflammatory insult towards epithelial neoplasia is less understood. In this issue of the JCI, Butin-Israeli et al. outline a mechanism whereby neutrophils control epithelial fitness and genomic instability via delivery of miR-23a–and miR-155–containing microparticles. Localized delivery of antisense oligonucleotides targeting miR-23a and miR-155 reversed this genomic instability and accelerated mucosal healing. This mechanism of neutrophil-derived microRNA shuttling opens up new therapeutic potential to enhance epithelial healing and limit mucosal injury.

Authors

Eóin N. McNamee

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Figure 1

Therapeutic blockade of neutrophil-derived microRNAs limits epithelial DNA double-strand breaks and enhances intestinal mucosal healing.

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Therapeutic blockade of neutrophil-derived microRNAs limits epithelial D...
Neutrophil recruitment is a cardinal sign of intestinal inflammation, such as is seen with ulcerative colitis or mucosal wounding, and is associated with increased cytokine production, MPO, and ROS production. (A) At the injury site, neutrophils deliver microparticles containing miR-123a and miR-155 to intestinal epithelial cells. These microRNAs promote degradation of the mRNAs encoding the nuclear envelop protein lamin B1 and the DNA mismatch repair protein RAD51, leading to an increase in epithelial genomic instability, delayed wound healing, and possible neoplastic transformation. (B) Microinjection of antisense oligonucleotides (ASOs) targeting miR-123a and miR-155 prevent these miRNAs from binding their targets, thereby restoring expression of RAD51 and lamin B1 mRNA, improving genomic stability and promoting wound repair.