|
AGEs/RAGE Axis in Diabetic Complications: A Review Study
|
Haniyeh Kazemi   , Hamideh Asadinezhde , Zakieh Shikhalishi , Ardeshir Nabizadeh Zolpirani |
|
|
|
Abstract: (215 Views) |
Introduction: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and is increasing at an alarming rate worldwide. The complications of diabetes mellitus are the leading cause of morbidity and mortality in affected individuals. The pathophysiology of the disease is complex, but AGEs (advanced glycation end products) are identified as key players in its progression and complications. Uncontrolled hyperglycemia is considered to be the principal cause of diabetic complications, as it leads to the production of AGEs.
Methods and Materials: This review article was prepared based on the findings of the search in Web of Science, PubMed, and Google Scholar databases from 2015 to 2022.
Results: There is evidence supporting a direct correlation between the AGEs/RAGE axis, activated signal transduction of mitogen-activated protein kinase (MAPK) and NFκB cascades, and intracellular ROS generation, which leads to the production of several inflammatory and profibrotic factors such as VCAM-1, ICAM-1, PAI-1, MCP-1, and MMP-2 protein. The increased expression of these factors is involved in arterial stiffness, vascular calcification, and plaque accumulation in atherosclerosis-prone vessels. The AGEs/RAGE axis also triggers a variety of signaling events. These downstream effectors include p38, SAPK/JNK, ERK1/2, and JAK/STAT pathway. The sustained activation of these pathways activates transcription factors such as NF-κB, STAT3, HIF-1α, and AP-1, which ultimately contribute to the pathophysiology of diabetes complications.
Conclusion: The engagement of RAGE by AGEs leads to sustained cellular dysfunction, known as "metabolic memory," which is associated with the pathogenesis of diabetes complications. Metabolic memory is a long-term influence of previously accumulated AGEs that can maintain RAGE over-expression and result in sustained activation of NFκB, prolonged induction of tissue-specific inflammation, and initiation and progression of long-term oxidative stress. |
|
| Keywords: diabetes mellitus, advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), diabetic complications |
|
|
Full-Text [PDF 330 kb]
(28 Downloads)
|
Type of Study: Research |
Subject:
General
Received: 2024/02/8 | Accepted: 2023/08/23 | Published: 2023/08/23
|
|
|
|
|
|
|
| Send email to the article author |
|
|
|
| Add your comments about this article |
|
|
|
