ArticleCell death discovery2020
MicroRNA-674-5p induced by HIF-1α targets XBP-1 in intestinal epithelial cell injury during endotoxemia.
Article in Cell death discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Unveiling Gut Homeostasis Disruption in Sepsis: Towards an Integrated Mechanistic and Translational Roadmap.Cell proliferation · 2026Review
- The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury.Cell stress & chaperones · 2025Article
- Hypoxia in the Pathophysiology of Inflammatory Bowel Disease.Comprehensive Physiology · 2023Article
- Differential Expression Profiles and Functional Prediction of circRNAs in Necrotizing Enterocolitis.BioMed research international · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal mucosal integrity dysfunction during endotoxemia can contribute to translocation of intestinal bacteria and a persistent systemic inflammatory response, which both fuel the pathophysiological development of sepsis or endotoxemia. The pathogenesis of intestinal damage induced by endotoxemia remains poorly understood. Here, we identified the microRNA (miR)-674-5p/X-box binding protein 1 (XBP-1) axis as a critical regulator and therapeutic target in preventing intestinal crypt cell proliferation during endotoxemia. MiR-674-5p was markedly increased in intestinal epithelial cells (IECs) during endotoxemia and its induction depended on hypoxia-inducible factor-1α (HIF-1α). Intriguingly, gene expression microanalysis revealed that expression of XBP-1 was down-regulated in IECs with over-expression of miR-674-5p. miR-674-5p was found to directly target XBP-1 protein expression. Upon in vitro, anti-miR-674-5p enhanced sXBP-1 expression and facilitated intestinal crypt cell proliferation. Blockade of miR-674-5p promoted XBP-1 activity, attenuated intestinal inflammation, and expedited intestinal regeneration, resulting in protection against endotoxemia-induced intestinal injury in mice. More importantly, the survival in endotoxemia mice was significantly improved by inhibiting intestinal miR-674-5p. Collectively, these data indicate that control of a novel miR-674-5p/XBP-1 signaling axis may mitigate endotoxemia -induced intestinal injury.
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