Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury.
2,3‐bisphosphoglycerate mutase (BPGM)
acute kidney injury (AKI)
glycolysis
inflammation
oxidative stress response
reactive oxygen species (ROS)
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
18 Oct 2024
18 Oct 2024
Historique:
revised:
02
10
2024
received:
14
08
2024
accepted:
03
10
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
18
10
2024
Statut:
aheadofprint
Résumé
2,3-bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney. A tubular-specific, doxycycline-inducible Bpgm-knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of Bpgm knockdown under osmotic stress. BPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of Bpgm resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, Bpgm knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules. BPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14242Subventions
Organisme : Deutsche Forschungsgemeinschaft
Organisme : Bundesministerium für Bildung und Forschung
Informations de copyright
© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.
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