ArticleJournal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract2017
Regulation of Postoperative Ileus by Lentivirus-Mediated HuR RNA Interference via the p38/MK2 Signaling Pathway.
Article in Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 5 citations in OpenAlex.
- Serum cytokine levels as markers of paralytic ileus following robotic radical prostatectomy at different pneumoperitoneum pressures.Current urology · 2021Article
- Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus.Theranostics · 2021Article
- Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.Frontiers in pharmacology · 2020Review
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
objectivesThe objective of the present study is to explore the effect of lentivirus-mediated HuR interference on the development and progression of postoperative ileus and the role of HuR in the regulation of the p38/MAPK-activated protein kinase-2 (MK2) signaling pathway during postoperative ileus.
methodsTo establish a mouse model of lentiviral transduction, we first determined the optimum effective titer of lentiviral vectors for transduction of the murine small intestine via the abdominal cavity by using hematoxylin and eosin (HE) staining, immunohistochemistry, detection of GFP messenger RNA (mRNA) and protein, and Western blotting. To investigate the effect of HuR interference on gene expression during postoperative ileus, we established a mouse model of postoperative ileus and used RT-PCR to measure the expression of proinflammatory genes, ELISA to measure the expression of serum inflammatory cytokines, immunohistochemistry to evaluate inflammatory cell infiltration in the small intestine, HE staining of paraffin sections to examine the pathology of the small intestine, and Western blotting to measure HuR expression and identify its role in the regulation of the p38/MK2 inflammatory pathway.
resultsWe successfully designed a mouse model of intraperitoneal transduction of HuR-RNAi lentivirus. When HuR gene expression was suppressed in a mouse model of postoperative ileus, the infiltration of inflammatory cells, the expression of proinflammatory genes, and the levels of serum inflammatory cytokines were significantly reduced. This reduction in inflammation correlated with reduced cytoplasmic localization of HuR and reduced activation of MK2.
conclusionsWithin the p38/MK2 signal transduction pathway, HuR may increase the mRNA stability of various inflammatory cytokines, thereby promoting inflammation that causes postoperative ileus. Suppressing the expression of HuR in a postoperative ileus model can effectively suppress the postoperative ileus inflammatory reaction. HuR might serve as a candidate drug target for the prevention and mitigation of postoperative ileus.
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