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Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion. | LitMetric

AI Article Synopsis

  • Intestinal ischemia-reperfusion (I/R) can cause serious complications like intestinal barrier breakdown, leading to increased mortality due to loss of tight junctions and heightened permeability.
  • Recombinant human angiopoietin-like protein 4 (rhANGPTL4) has shown promise in protecting blood-brain barriers and appears to mitigate intestinal injuries caused by I/R, as indicated by positive changes in various health markers.
  • The study found that rhANGPTL4 treatment not only reversed negative indicators related to I/R but also reduced inflammation, oxidative stress, and cell death, suggesting it could be a novel therapy for improving outcomes in patients with intestinal barrier deterioration.

Article Abstract

Background: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury.

Aim: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.

Methods: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R .

Results: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.

Conclusion: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival maintenance of intestinal barrier structure and functions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409166PMC
http://dx.doi.org/10.3748/wjg.v27.i32.5404DOI Listing

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