Roles of Nrf2 in Protecting the Kidney from Oxidative Damage.
Animals
Animals, Genetically Modified
Clinical Trials as Topic
Disease Management
Disease Models, Animal
Disease Susceptibility
Gene Expression Regulation
Humans
Kidney
/ metabolism
Kidney Diseases
/ etiology
NF-E2-Related Factor 2
/ genetics
Oxidative Stress
/ genetics
Patient Outcome Assessment
Signal Transduction
Nrf2-activating compounds
chronic kidney disease
erythropoietin
ischemia-reperfusion injury
kidney fibrosis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Apr 2020
22 Apr 2020
Historique:
received:
18
03
2020
revised:
16
04
2020
accepted:
21
04
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
26
1
2021
Statut:
epublish
Résumé
Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in treating kidney disease. Therefore, elucidating the complicated molecular pathology of kidney disease is an urgent priority for developing innovative therapeutics for kidney disease. Recent studies demonstrated that intertwined renal vasculature often causes ischemia-reperfusion injury (IRI), which generates oxidative stress, and that the accumulation of oxidative stress is a common pathway underlying various types of kidney disease. We reported that activating the antioxidative transcription factor Nrf2 in renal tubules in mice with renal IRI effectively mitigates tubular damage and interstitial fibrosis by inducing the expression of genes related to cytoprotection against oxidative stress. Additionally, since the kidney performs multiple functions beyond blood purification, renoprotection by Nrf2 activation is anticipated to lead to various benefits. Indeed, our experiments indicated the possibility that Nrf2 activation mitigates anemia, which is caused by impaired production of the erythroid growth factor erythropoietin from injured kidneys, and moderates organ damage worsened by anemic hypoxia. Clinical trials investigating Nrf2-activating compounds in kidney disease patients are ongoing, and beneficial effects are being obtained. Thus, Nrf2 activators are expected to emerge as first-in-class innovative medicine for kidney disease treatment.
Identifiants
pubmed: 32331329
pii: ijms21082951
doi: 10.3390/ijms21082951
pmc: PMC7215459
pii:
doi:
Substances chimiques
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Chugai Pharmaceutical
ID : NA
Organisme : Daiichi Sankyo Foundation of Life Science
ID : NA
Organisme : Takeda Science Foundation
ID : NA
Organisme : SENSHIN Medical Research Foundation
ID : NA
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