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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion
Zi-Yi Wang, Jian-Yu Lin, Yang-Rong Feng, De-Shun Liu, Xu-Zi Zhao, Tong Li, Si-Yuan Li, Jing-Chao Sun, Shu-Feng Li, Wen-Yan Jia, Hui-Rong Jing
Zi-Yi Wang, Emergent Intensive Care Unit, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Jian-Yu Lin, Department of Gastrointestinal Surgery, Weihai Central Hospital, Weihai 264200, Shandong Province, China
Yang-Rong Feng, Graduate College, Shandong First Medical University, Jinan 271000, Shandong Province, China
De-Shun Liu, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China
Xu-Zi Zhao, Department of Pharmacology, Dalian Medical University, Dalian 116044, Liaoning Province, China
Tong Li, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100000, China
Si-Yuan Li, Jing-Chao Sun, Shu-Feng Li, Hui-Rong Jing, Department of General Surgery, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
Wen-Yan Jia, Physiological Examination Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Author contributions: Wang ZY, Jing HR and Lin JY designed the study; Jing HR and Wang ZY supervised the study; Liu DS, Zhao XZ and Sun JC collected and analyzed the data; Li SY and Feng YR performed the R Script; Lin JY and Li SF and Jia WY prepared the figures and drafted the manuscript; Jing HR and Li Tong revised the manuscript for important intellectual content; Jing HR and Jia WY contributed equally as co-corresponding authors; all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81600446; the Science and Technology of Traditional Chinese Medicine Foundation in Qingdao, No. 2021-zyyz03; and the Science and technology development of Medicine and health Foundation in Shandong Province, China, No. 202004010508.
Institutional animal care and use committee statement: The study was reviewed and approved by the Dalian Medical University Institutional Review Board (Approval No. L20190232).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hui-Rong Jing, MD, PhD, Associate Professor, Surgeon, Department of General Surgery, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Southern District, Qingdao 266071, Shandong Province, China. jhrdlmu_edu@126.com
Received: April 24, 2021
Peer-review started: April 24, 2021
First decision: June 3, 2021
Revised: June 17, 2021
Accepted: July 30, 2021
Article in press: July 30, 2021
Published online: August 28, 2021
ARTICLE HIGHLIGHTS
Research background
Intestinal barrier breakdown remains frequently complicated in critical care patients of intestinal ischemia-reperfusion (I/R), severe acute pancreatitis and sepsis. Although vigorous experiments are performed in this field, the application of an instant effective agent or therapy in clinical has not yet been discovered. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is known to be protective to the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates intestinal injury.
Research motivation
We intend to explore and discover a novel and promising agent to confer intestinal barrier protection induced by I/R. Our results indicated recombinant agents that exhibit intestinal barrier protective characteristics. The agents may be safer and facilitated to translate into clinical use.
Research objectives
Understanding and regulating ANGPTL4 as a therapeutic target and recombinant human ANGPTL4 will be an application in clinical use in patients suffering from intestinal barrier dysfunction.
Research methods
This research was executed using Wistar rats treated with intestinal I/R and intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells stimulated with H/R to intimate the I/R pathogenesis in vivo. Further, RNA interference was performed, and recombinant ANGPTL4 has been evaluated.
Research results
A loss of crypt epithelium and myocytes were observed in the muscularis propria. Intraluminal microdialysis were changed, as well as the biochemistry indicators were remarkably enhanced following intestinal I/R. Recombinant human ANGPTL4 treatment significantly reversed indicators above associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and was associated with an improvement of survival rate. In vitro studies showed similar results in Caco-2 and human umbilical vein endothelial cells.
Research conclusions
Recombinant human ANGPTL4 achieved an optimal therapeutic effect for intestinal I/R-induced intestinal barrier injury. Using this model, the intestinal barrier structure and functions indicators were maintained, thus providing a promising therapeutic potential.
Research perspectives
ANGPTL4 may be a valuable predictor, and similar research in patients who suffered critical care conditions could be evaluated.
