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RAGE pathway activation and function in chronic kidney disease and COVID-19
Colleen S Curran1, Jeffrey B Kopp2
1Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
Frontiers in Medicine
|August 26, 2022
Summary
The receptor for advanced glycation end-products (RAGE) plays a key role in kidney disease and COVID-19. Targeting RAGE may offer new treatments for progressive kidney conditions.
Area of Science:
- Nephrology
- Immunology
- Infectious Diseases
Background:
- The receptor for advanced glycation end-products (RAGE) and its ligands are implicated in various diseases, including autoimmunity, cancer, and infections.
- RAGE activation is heightened in chronic kidney disease (CKD) and coronavirus disease 2019 (COVID-19), with potential links between CKD, COVID-19 severity, and long COVID.
- RAGE is present in all kidney cell types, and its increased production in CKD and COVID-19 exacerbates RAGE activity.
Purpose of the Study:
- To review the role and mechanisms of RAGE and its ligands in the context of kidney disease and COVID-19.
- To explore potential therapeutic strategies targeting the RAGE pathway for kidney diseases.
Main Methods:
- Review of existing literature on RAGE, RAGE ligands, CKD, and COVID-19.
- Discussion of the cellular and molecular mechanisms underlying RAGE activation and its consequences in kidney injury.
- Analysis of preclinical data on RAGE-targeting small molecules in animal models.
Main Results:
- Increased RAGE activity in CKD and COVID-19 contributes to cellular dysfunction, tissue damage, fibrosis, and inflammation.
- These pathological processes lead to kidney function decline, hypertension, thrombotic issues, and cognitive impairment.
- Animal models show that small molecules can antagonize RAGE activity.
Conclusions:
- RAGE signaling is a significant factor in the progression of kidney disease and its exacerbation by COVID-19.
- Targeting RAGE, its co-receptors, or ligands presents a promising therapeutic avenue.
- Such targeted therapies could potentially slow or halt the progression of kidney disease, addressing limitations of current treatments.
Keywords:
High-mobility group box 1S100A8S100A9complement C1qlysophosphatidic acidmacrophage antigen 1receptor for advanced glycation end-productsurokinase-type plasminogen activator receptorMore Related Videos
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