Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2023; 14(1): 48-61
Published online Jan 15, 2023. doi: 10.4239/wjd.v14.i1.48
Gut region-specific TNFR expression: TNFR2 is more affected than TNFR1 in duodenal myenteric ganglia of diabetic rats
Bence Pál Barta, Benita Onhausz, Afnan AL Doghmi, Zita Szalai, János Balázs, Mária Bagyánszki, Nikolett Bódi
Bence Pál Barta, Benita Onhausz, Afnan AL Doghmi, Zita Szalai, János Balázs, Mária Bagyánszki, Nikolett Bódi, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged 6726, Hungary
Author contributions: Bódi N and Bagyánszki M designed the study; Barta BP, Bódi N, Onhausz B, AL Doghmi A, Balázs J and Szalai Z performed the research; Barta BP and Bódi N analyzed the data; Bódi N wrote the original draft; Barta BP and Bagyánszki M reviewed and edited the original draft; Bódi N and Bagyánszki M prepared the figures; all authors have read and approve the final manuscript.
Supported by Hungarian National Research, Development and Innovation Fund Projects, No. GINOP-2.3.3-15-2016-00006; Hungarian NKFIH Fund Project, No. FK131789 (to Bódi N); János Bolyai Research Scholarship of the Hungarian Academy of Sciences (to Bódi N); ÚNKP-21-5 - New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (to Bódi N); and Gedeon Richter Plc Centenary Foundation (to Bódi N).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the National Scientific Ethical Committee on Animal Experimentation (National Competent Authority), with the license number XX./1636/2019.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available from the corresponding author at bmarcsi@bio.u-szeged.hu.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mária Bagyánszki, PhD, Associate Professor, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged 6726, Hungary. bmarcsi@bio.u-szeged.hu
Received: July 5, 2022
Peer-review started: July 5, 2022
First decision: July 31, 2022
Revised: August 16, 2022
Accepted: October 27, 2022
Article in press: October 27, 2022
Published online: January 15, 2023
Processing time: 188 Days and 19.6 Hours
ARTICLE HIGHLIGHTS
Research background

Tumor necrosis factor alpha plays an essential role in inflammatory modulation of enteric neurons, however, it can promote apoptosis or cell survival depending on its different receptors (TNFR1 and TNFR2).

Research motivation

Distinct neuronal microenvironment is critical in gut segment-specific diabetic enteric neuropathy, therefore, the region-dependent expression and alterations of different TNFRs may also be important in therapy targeting motility disturbances in type 1 diabetes.

Research objectives

To investigate the TNFR1 and TNFR2 expression in myenteric ganglia and their environment in different intestinal regions of diabetic rats.

Research methods

Double-labeling fluorescent immunohistochemistry, post-embedding immunogold electron microscopy and enzyme-linked immunosorbent assay were applied to evaluate the TNFR1 and TNFR2 expression in myenteric ganglia and muscle/myenteric plexus tissue homogenates from different gut segments of streptozotocin-induced diabetic, insulin-treated diabetic and control rats.

Research results

TNFRs expression displayed a strictly region-specific pattern even in control animals. However, among all the investigated gut segments, only the duodenum showed significant alterations of TNFR expression in diabetic rats. The TNFR2 density was decreased in the myenteric ganglia, while no significant changes in TNFR1 density were revealed. Moreover, the TNFR2/TNFR1 proportion was markedly influenced in both the ganglia and their muscular environment of diabetics. Insulin had controversial effects on TNFR expression.

Research conclusions

Diabetes-related region-specificity in TNFRs expression shows that TNFR2 is more affected than TNFR1 in duodenal myenteric ganglia of type 1 diabetic rats.

Research perspectives

Nuclear factor-kappa B has a key role in TNFR2 signaling pathway. Therefore, evaluation of the involvement of nuclear factor-kappa B in region-dependent diabetic enteric neuropathy may be important in the future.