Limonin, a natural ERK2 agonist, protects against ischemic acute kidney injury.
acute kidney injury
cell death
cell proliferation
extracellular signal-regulated kinase 2
limonin
Journal
International journal of biological sciences
ISSN: 1449-2288
Titre abrégé: Int J Biol Sci
Pays: Australia
ID NLM: 101235568
Informations de publication
Date de publication:
2023
2023
Historique:
received:
05
01
2023
accepted:
11
05
2023
medline:
19
6
2023
pubmed:
16
6
2023
entrez:
16
6
2023
Statut:
epublish
Résumé
Acute kidney injury (AKI) is a refractory clinical syndrome with limited effective treatments. Amid AKI, activation of the extracellular signal-regulated kinase (ERK) cascade plays a critical role in promoting kidney repair and regeneration. However, a mature ERK agonist in treating kidney disease remains lacking. This study identified limonin, a member of the class of compounds known as furanolactones, as a natural ERK2 activator. Employing a multidisciplinary approach, we systemically dissected how limonin mitigates AKI. Compared to vehicles, pretreatment of limonin significantly preserved kidney functions after ischemic AKI. We revealed that ERK2 is a significant protein linked to the limonin's active binding sites through structural analysis. The molecular docking study showed a high binding affinity between limonin and ERK2, which was confirmed by the cellular thermal shift assay and microscale thermophoresis. Mechanistically, we further validated that limonin promoted tubular cell proliferation and reduced cell apoptosis after AKI by activating ERK signaling pathway
Identifiants
pubmed: 37324945
doi: 10.7150/ijbs.82417
pii: ijbsv19p2860
pmc: PMC10266085
doi:
Substances chimiques
limonin
L0F260866S
Limonins
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2860-2878Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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