Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2021; 12(5): 658-672
Published online May 15, 2021. doi: 10.4239/wjd.v12.i5.658
Diabetes-related intestinal region-specific thickening of ganglionic basement membrane and regionally decreased matrix metalloproteinase 9 expression in myenteric ganglia
Nikolett Bódi, Diána Mezei, Payal Chakraborty, Zita Szalai, Bence Pál Barta, János Balázs, Zsolt Rázga, Edit Hermesz, Mária Bagyánszki
Nikolett Bódi, Diána Mezei, Zita Szalai, Bence Pál Barta, János Balázs, Mária Bagyánszki, Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged 6726, Hungary
Payal Chakraborty, Edit Hermesz, Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged 6726, Hungary
Zsolt Rázga, Department of Pathology, Faculty of Medicine, University of Szeged, Szeged 6720, Hungary
Author contributions: Bódi N was responsible for the conceptualization, methodology, investigation, writing, funding acquisition; Mezei D, Barta BP, Chakraborty P were responsible for the investigation, formal analysis; Szalai Z was responsible for the visualization; Balázs J was responsible for the validation; Hermesz E was responsible for the validation, supervision; Rázga Z was responsible for the resources; Bagyánszki M was responsible for the visualization, writing-review and editing, supervision.
Supported by European Union and the Hungarian Government in the framework, No. EFOP-3.6.1-16-2016-00008; Hungarian NKFIH fund project, No. FK131789 (to Bódi N); János Bolyai Research Scholarship of the Hungarian Academy of Sciences (to Bódi N); and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, No. ÚNKP-20-5 (to Bódi N).
Institutional review board statement: The study was reviewed and approved by Csaba Varga, the head of Dept. of Physiology, Anatomy and Neuroscience.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: I certify that there is no actual or potential conflict of interest in relation to this article.
Data sharing statement: Dataset available from the corresponding author at bmarcsi@bio.u-szeged.hu e-mail address.
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: Mária Bagyánszki, PhD, Associate Professor, Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, Szeged 6726, Hungary. bmarcsi@bio.u-szeged.hu
Received: February 2, 2021
Peer-review started: February 2, 2021
First decision: February 27, 2021
Revised: March 10, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: May 15, 2021
Processing time: 92 Days and 14.4 Hours
ARTICLE HIGHLIGHTS
Research background

The diabetic damage of enteric neurons and intestinal capillaries supplying the enteric ganglia are strictly intestinal region dependent. Therefore, the underlying molecular differences in the neuronal environment should be more emphasized.

Research motivation

To prove the presence of essential regional differences in the neuronal milieu which may explain the gut segment-specific enteric neuropathy and vascular dysfunction.

Research objectives

To reveal the impact of diabetes and immediate insulin treatment on the thickness of basement membrane (BM) surrounding myenteric ganglia, as well as the expression of matrix metalloproteinase 9 (MMP9) and its tissue inhibitor of metalloproteinase 1 (TIMP1) which are key players in regulating extracellular matrix dynamics.

Research methods

Electron microscopic morphometry, fluorescent and gold-labelling immunohistochemistry and quantitative polymerase chain reaction were applied to study the myenteric ganglia and their environment in the different gut segments of diabetic, insulin-treated diabetic and control rats.

Research results

In the diabetic ileum, the ganglionic BM was significantly thickened which was prevented by insulin treatment. These changes were also reflected in a decrease in MMP9/TIMP1 ratio in ileal myenteric ganglia. However, in the duodenum of diabetics neither the ganglionic BM thickness nor the MMP9/TIMP1 ratio were changed.

Research conclusions

Regionally decreased MMP9 expression in ganglia and region-dependent ganglionic BM thickening correlate well with intestinal segment-specific enteric neuropathy.

Research perspectives

Based on these findings in type 1 diabetic rat model, we are planning to expand our investigations to type 2 diabetes in the future.