Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury.
Acute kidney injury
High-mobility group box 1 (HMGB1)
Ischemia and reperfusion
Receptor for advanced glycation end products (RAGE)
Soluble receptor for advanced glycation end products (sRAGE)
Journal
Biology open
ISSN: 2046-6390
Titre abrégé: Biol Open
Pays: England
ID NLM: 101578018
Informations de publication
Date de publication:
15 01 2022
15 01 2022
Historique:
received:
25
05
2021
accepted:
11
11
2021
pubmed:
24
11
2021
medline:
5
4
2022
entrez:
23
11
2021
Statut:
ppublish
Résumé
The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type (WT) control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.
Identifiants
pubmed: 34812852
pii: 273473
doi: 10.1242/bio.058852
pmc: PMC8822355
pii:
doi:
Substances chimiques
Protein Isoforms
0
Receptor for Advanced Glycation End Products
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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