Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury.

Autor:	Kulow VA; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany.; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Roegner K; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Labes R; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Kasim M; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Mathia S; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany.; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Czopek CS; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Berndt N; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.; Deutsches Herzzentrum der Charité (DHZC), Institute of Computer-assisted Cardiovascular Medicine, Berlin, Germany.; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Becker PN; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Ter-Avetisyan G; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Luft FC; Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Enghard P; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany., Hinze C; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany.; Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany., Klocke J; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany., Eckardt KU; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany., Schmidt-Ott KM; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany.; Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany., Persson PB; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany., Rosenberger C; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin (CCM), Berlin, Germany., Fähling M; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Translationale Physiologie (CCM), Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Oct 18, pp. e14242. Date of Electronic Publication: 2024 Oct 18.
DOI:	10.1111/apha.14242
Abstrakt:	Aim: 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. Methods: 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. Results: 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. Conclusion: 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. (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze:	MEDLINE
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