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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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- Porosk, Rando (author)
- Soomets, Ursel (author)
- Howell, Brian W (author)
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- (creator_code:org_t)
- 2020-12-17
- 2020
- English.
- In: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:24
- Journal article (peer-reviewed)
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)
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- Borén, Jan, 1963
- Porosk, Rando
- Soomets, Ursel
- Pedrelli, Matteo
- Parini, Paolo
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