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Depletion of protei...
Depletion of protein kinase STK25 ameliorates renal lipotoxicity and protects against diabetic kidney disease.
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- Cansby, Emmelie, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Caputo, Mara (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Gao, Lei (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Kulkarni, Nagaraj M. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Nerstedt, Annika, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Ståhlman, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Porosk, Rando (author)
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Soomets, Ursel (author)
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- Pedrelli, Matteo (author)
- Karolinska Institutet
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- Parini, Paolo (author)
- Karolinska Institutet
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- Marschall, Hanns-Ulrich, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Nyström, Jenny, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Howell, Brian W (author)
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- Mahlapuu, Margit, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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(creator_code:org_t)
- 2020-12-17
- 2020
- English.
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In: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:24
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Abstract
Subject headings
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- Diabetic kidney disease (DKD) is the most common cause of severe renal disease worldwide and the single strongest predictor of mortality in diabetes patients. Kidney steatosis has emerged as a critical trigger in the pathogenesis of DKD; however, the molecular mechanism of renal lipotoxicity remains largely unknown. Our recent studies in genetic mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine protein kinase (STK)25 as a critical regulator of ectopic lipid storage in several metabolic organs prone to diabetic damage. Here, we demonstrate that overexpression of STK25 aggravates renal lipid accumulation and exacerbates structural and functional kidney injury in a mouse model of DKD. Reciprocally, inhibiting STK25 signaling in mice ameliorates diet-induced renal steatosis and alleviates the development of DKD-associated pathologies. Further, we find that STK25 silencing in human kidney cells protects against lipid deposition as well as oxidative and endoplasmic reticulum stress. Together, our results suggest that STK25 regulates a critical node governing susceptibility to renal lipotoxicity and that STK25 antagonism could mitigate DKD progression.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Cansby, Emmelie, ...
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Caputo, Mara
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Gao, Lei
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Kulkarni, Nagara ...
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Nerstedt, Annika ...
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Ståhlman, Marcus ...
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show more...
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Borén, Jan, 1963
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Porosk, Rando
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Soomets, Ursel
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Pedrelli, Matteo
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Parini, Paolo
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Marschall, Hanns ...
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Nyström, Jenny, ...
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Howell, Brian W
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Mahlapuu, Margit ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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JCI insight
- By the university
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University of Gothenburg
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Karolinska Institutet