Robles-Osorio ML, Sabath E. Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review. World J Diabetes 2023; 14(7): 1013-1026 [PMID: 37547580 DOI: 10.4239/wjd.v14.i7.1013]
Corresponding Author of This Article
Ernesto Sabath, MD, PhD, Assistant Professor, Director, Renal and Metabolism Unit, Hospital General de Querétaro, Adalberto Martínez 448, Queretaro 76180, Mexico. esabath@yahoo.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Diabetes. Jul 15, 2023; 14(7): 1013-1026 Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.1013
Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review
Ma Ludivina Robles-Osorio, Ernesto Sabath
Ma Ludivina Robles-Osorio, Nutrition School, Universidad Autónoma de Querétaro, Queretaro 76230, Mexico
Ernesto Sabath, Renal and Metabolism Unit, Hospital General de Querétaro, Queretaro 76180, Mexico
Ernesto Sabath, Department of Nutrition, Universidad Autónoma de Queretaro, Queretaro 76230, Mexico
Author contributions: Robles-Osorio ML and Sabath E designed the research study, performed the review of the literature and the article selection; Sabath E wrote the manuscript; Both authors read and approved the final manuscript.
Conflict-of-interest statement: No potential nor real competing interests were reported by the authors.
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: Ernesto Sabath, MD, PhD, Assistant Professor, Director, Renal and Metabolism Unit, Hospital General de Querétaro, Adalberto Martínez 448, Queretaro 76180, Mexico. esabath@yahoo.com
Received: January 28, 2023 Peer-review started: January 28, 2023 First decision: March 14, 2023 Revised: March 20, 2023 Accepted: May 23, 2023 Article in press: May 23, 2023 Published online: July 15, 2023
Abstract
The chronic complications of diabetes mellitus constitute a major public health problem. For example, diabetic eye diseases are the most important cause of blindness, and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide. The cellular and molecular mechanisms of these chronic complications are still poorly understood, preventing the development of effective treatment strategies. Tight junctions (TJs) are epithelial intercellular junctions located at the most apical region of cell-cell contacts, and their main function is to restrict the passage of molecules through the paracellular space. The TJs consist of over 40 proteins, and the most important are occludin, claudins and the zonula occludens. Accumulating evidence suggests that TJ disruption in different organs, such as the brain, nerves, retina and kidneys, plays a fundamental pathophysiological role in the development of chronic complications. Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy, brain injury and diabetic retinopathy. The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown. In the present review, we highlighted the molecular events that lead to barrier dysfunction in diabetes. Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.
Core Tip: Chronic complications of diabetes mellitus constitute a major public health problem. Tight junctions are epithelial intercellular junctions, and their main function is to restrict the passage of molecules through the paracellular space. TJ disruption plays a fundamental pathophysiological role in the development of diabetic chronic complications. Increased permeability of the blood-brain barrier and the blood-retinal barrier are related to development of diabetic neuropathy and diabetic retinopathy.
