Magalhães HIR, Machado FA, Souza RF, Caetano MAF, Figliuolo VR, Coutinho-Silva R, Castelucci P. Study of the roles of caspase-3 and nuclear factor kappa B in myenteric neurons in a P2X7 receptor knockout mouse model of ulcerative colitis. World J Gastroenterol 2023; 29(22): 3440-3468 [PMID: 37389242 DOI: 10.3748/wjg.v29.i22.3440]
Corresponding Author of This Article
Patricia Castelucci, MHSc, PhD, Associate Professor, Associate Research Scientist, Lecturer, Department of Anatomy, University of São Paulo, 2415, Av. Dr Lineu Prestes, São Paulo 05508-000, Brazil. pcastel@usp.br
Research Domain of This Article
Anatomy & Morphology
Article-Type of This Article
Basic Study
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Magalhães HIR, Machado FA, Souza RF, Caetano MAF, Figliuolo VR, Coutinho-Silva R, Castelucci P. Study of the roles of caspase-3 and nuclear factor kappa B in myenteric neurons in a P2X7 receptor knockout mouse model of ulcerative colitis. World J Gastroenterol 2023; 29(22): 3440-3468 [PMID: 37389242 DOI: 10.3748/wjg.v29.i22.3440]
Henrique Inhauser Riceti Magalhães, Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo 05508-270, Brazil
Felipe Alexandre Machado, Roberta Figueiroa Souza, Marcos Antônio Ferreira Caetano, Patricia Castelucci, Department of Anatomy, University of São Paulo, São Paulo 05508-000, Brazil
Vanessa Ribeiro Figliuolo, Robson Coutinho-Silva, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Author contributions: Magalhães HIR was responsible for the literature review and analysis and wrote the manuscript; Machado FA, Souza RF, Caetano MAF, Figliuolo VR, and Coutinho-Silva R helped with acquisition, analysis and interpretation of data and made critical suggestions about the writing; Castelucci P designed the study, helped with acquisition, analysis and interpretation of data, performed the critical interpretation and revised the manuscript for intellectual content; and all authors approved the final version of the manuscript.
Supported bythe National Council for Scientific and Technological Development, No. 168015/2018-8; and the São Paulo Research Foundation, No. 2014/25927-2 and No. 2018/07862-1.
Institutional review board statement: The study was reviewed and approved by the pela Comissão de Ética no Uso de Animais da Instituto de Ciências Biomédicas Universidade de São Paulo (Approval No. CEUA 2372300921).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethic Committee on Animal Use of the School of Veterinary Medicine and Animal Science University of São Paulo (Approval No. CEUA 2841270120).
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at pcastel@usp.br. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Corresponding author: Patricia Castelucci, MHSc, PhD, Associate Professor, Associate Research Scientist, Lecturer, Department of Anatomy, University of São Paulo, 2415, Av. Dr Lineu Prestes, São Paulo 05508-000, Brazil. pcastel@usp.br
Received: February 27, 2023 Peer-review started: February 27, 2023 First decision: April 3, 2023 Revised: April 25, 2023 Accepted: May 12, 2023 Article in press: May 12, 2023 Published online: June 14, 2023 Processing time: 99 Days and 7.3 Hours
ARTICLE HIGHLIGHTS
Research background
Inflammation affects enteric neurons and has P2X7 receptor signaling.
Research motivation
The motivation of the work was to study the mechanisms of nuclear factor kappa B (NF-κB) and caspase-3.
Research objectives
To study calretinin-positive neurons and caspase-3 and NF-κB pathways in intestinal inflammation.
Research methods
Research methods of immunohistochemistry, morphometry, conventional histology and transmission electron microscopy were used.
Research results
There was a decrease in calretinin neurons in wild type colitis (WT) animals and recovery of neurons in mice deficient for the P2X7 receptor (KO). There was an increase in caspase-3 and NF-κB pathways in the WT colitis and recovery animals in the KO groups.
Research conclusions
The P2X7 receptor is involved in the decrease of neurons in the WT colitis group, and this receptor could be a therapeutic target.
Research perspectives
The perspective of the work is to use other techniques to explain other pathways of action mechanisms.
