Journal Article

DKFZ-2022-01246

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.

Garreta, E. ; Prado, P. ; Stanifer, M. L.DKFZ* ; Monteil, V. ; Marco, A. ; Ullate-Agote, A. ; Moya-Rull, D. ; Vilas-Zornoza, A. ; Tarantino, C. ; Romero, J. P. ; Jonsson, G. ; Oria, R. ; Leopoldi, A. ; Hagelkruys, A. ; Gallo, M. ; González, F. ; Domingo-Pedrol, P. ; Gavaldà, A. ; Del Pozo, C. H. ; Hasan Ali, O. ; Ventura-Aguiar, P. ; Campistol, J. M. ; Prosper, F. ; Mirazimi, A. ; Boulant, S.DKFZ* ; Penninger, J. M. ; Montserrat, N.

2022
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.cmet.2022.04.009

Abstract: 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.

Keyword(s): Angiotensin-Converting Enzyme 2 (MeSH) ; COVID-19 (MeSH) ; Diabetes Mellitus (MeSH) ; Diabetic Nephropathies (MeSH) ; Humans (MeSH) ; Kidney: metabolism (MeSH) ; Organoids (MeSH) ; Peptidyl-Dipeptidase A: genetics (MeSH) ; Peptidyl-Dipeptidase A: metabolism (MeSH) ; SARS-CoV-2 (MeSH) ; ACE2 ; COVID-19 ; SARS-CoV-2 ; angiotensin-converting enzyme 2 ; diabetes 2 ; human kidney organoids ; Peptidyl-Dipeptidase A ; Angiotensin-Converting Enzyme 2

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Contributing Institute(s):

1. F140 Zelluläre Polarität und virale Infektion (F140)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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