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Autor
Bleyer, Anthony J 1 Chen, Ying Maggie 1 Duffield, Jeremy S 1 Fang, Yili 1 Gu, Chenjian 1 Jackrel, Meredith E 1 Johnson, Bryce G 1 Kidd, Kendrah 1 Kim, Yeawon 1 Kmoch, Stanislav 1 Li, Chuang 1 Lindahl, Maria 1 Park, Sun-Ji 1 Pietka, Terri A 1 Puri, Anuradhika 1 Sharma, Vijay 1 Sivapackiam, Jothilingam 1 Tycksen, Eric 1 Urano, Fumihiko 1
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Pracoviště
Department of Biomedical Engineering ... 1 Department of Cell Biology and Physio... 1 Department of Chemistry Washington Un... 1 Department of Neurology Washington Un... 1 Division of Endocrinology Metabolism ... 1 Division of Nephrology Department of ... 1 Genome Technology Access Center McDon... 1 Institute of Biotechnology HiLIFE Uni... 1 Mallinckrodt Institute of Radiology W... 1 Nutrition and Geriatrics Division Was... 1 Pfizer Worldwide Research and Develop... 1 Prime Medicine Inc Cambridge MA USA 1 Research Unit of Rare Diseases Depart... 1 Section of Nephrology Wake Forest Uni... 1
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Autor
Bleyer, Anthony J 1 Chen, Ying Maggie 1 Duffield, Jeremy S 1 Fang, Yili 1 Gu, Chenjian 1 Jackrel, Meredith E 1 Johnson, Bryce G 1 Kidd, Kendrah 1 Kim, Yeawon 1 Kmoch, Stanislav 1 Li, Chuang 1 Lindahl, Maria 1 Park, Sun-Ji 1 Pietka, Terri A 1 Puri, Anuradhika 1 Sharma, Vijay 1 Sivapackiam, Jothilingam 1 Tycksen, Eric 1 Urano, Fumihiko 1
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Pracoviště
Department of Biomedical Engineering ... 1 Department of Cell Biology and Physio... 1 Department of Chemistry Washington Un... 1 Department of Neurology Washington Un... 1 Division of Endocrinology Metabolism ... 1 Division of Nephrology Department of ... 1 Genome Technology Access Center McDon... 1 Institute of Biotechnology HiLIFE Uni... 1 Mallinckrodt Institute of Radiology W... 1 Nutrition and Geriatrics Division Was... 1 Pfizer Worldwide Research and Develop... 1 Prime Medicine Inc Cambridge MA USA 1 Research Unit of Rare Diseases Depart... 1 Section of Nephrology Wake Forest Uni... 1
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"R21 DK131557" Dotaz Zobrazit nápovědu
Free Medical Journals od 2010
Nature Open Access od 2010-12-01
PubMed Central od 2012
Europe PubMed Central od 2012
ProQuest Central od 2010-01-01
Open Access Digital Library od 2015-01-01
Open Access Digital Library od 2015-01-01
Medline Complete (EBSCOhost) od 2012-11-01
Health & Medicine (ProQuest) od 2010-01-01
ROAD: Directory of Open Access Scholarly Resources od 2010
PubMed
37838725
DOI
10.1038/s41467-023-42154-0
Knihovny.cz E-zdroje
Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), a leading hereditary kidney disease. There are no targeted therapies. In our generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are impaired, leading to cGAS-STING activation and tubular injury. Moreover, we demonstrate that inducible tubular overexpression of mesencephalic astrocyte-derived neurotrophic factor (MANF), a secreted endoplasmic reticulum protein, after the onset of disease stimulates autophagy/mitophagy, clears mutant UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, thus protecting kidney function in our ADTKD mouse model. Conversely, genetic ablation of MANF in the mutant thick ascending limb tubular cells worsens autophagy suppression and kidney fibrosis. Together, we have discovered MANF as a biotherapeutic protein and elucidated previously unknown mechanisms of MANF in the regulation of organelle homeostasis, which may have broad therapeutic applications to treat various proteinopathies.
- MeSH
- autofagie genetika MeSH
- fibróza MeSH
- homeostáza MeSH
- lidé MeSH
- myši MeSH
- neurotrofní faktory genetika MeSH
- polycystická choroba ledvin * MeSH
- zvířata MeSH
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- lidé MeSH
- myši MeSH
- zvířata MeSH
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- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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