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A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral...

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Main Authors: Garreta, Elena (Author) , Prado, Patricia (Author) , Stanifer, Megan (Author) , Monteil, Vanessa (Author) , Marco, Andrés (Author) , Ullate-Agote, Asier (Author) , Moya-Rull, Daniel (Author) , Vilas-Zornoza, Amaia (Author) , Tarantino, Carolina (Author) , Romero, Juan Pablo (Author) , Jonsson, Gustav (Author) , Oria, Roger (Author) , Leopoldi, Alexandra (Author) , Hagelkruys, Astrid (Author) , Gallo, Maria (Author) , González, Federico (Author) , Domingo-Pedrol, Pere (Author) , Gavaldà, Aleix (Author) , Pozo, Carmen Hurtado del (Author) , Hasan Ali, Omar (Author) , Ventura-Aguiar, Pedro (Author) , Campistol, Josep María (Author) , Prosper, Felipe (Author) , Mirazimi, Ali (Author) , Boulant, Steeve (Author) , Penninger, Josef M. (Author) , Montserrat, Nuria (Author)
Format: Article (Journal)
Language:English
Published: 12 May 2022
In: Cell metabolism
Year: 2022, Volume: 34, Issue: 6, Pages: 857-873, e1-e9
ISSN:1932-7420
DOI:10.1016/j.cmet.2022.04.009
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cmet.2022.04.009
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S155041312200136X
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Author Notes:Elena Garreta, Patricia Prado, Megan L. Stanifer, Vanessa Monteil, Andrés Marco, Asier Ullate-Agote, Daniel Moya-Rull, Amaia Vilas-Zornoza, Carolina Tarantino, Juan Pablo Romero, Gustav Jonsson, Roger Oria, Alexandra Leopoldi, Astrid Hagelkruys, Maria Gallo, Federico González, Pere Domingo-Pedrol, Aleix Gavaldà, Carmen Hurtado del Pozo, Omar Hasan Ali, Pedro Ventura-Aguiar, Josep María Campistol, Felipe Prosper, Ali Mirazimi, Steeve Boulant, Josef M. Penninger, and Nuria Montserrat
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Summary:It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.
Item Description:Gesehen am 31.08.2022
Physical Description:Online Resource
ISSN:1932-7420
DOI:10.1016/j.cmet.2022.04.009

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