%0 Journal Article
%A Garreta, Elena
%A Prado, Patricia
%A Stanifer, Megan L
%A Monteil, Vanessa
%A Marco, Andrés
%A Ullate-Agote, Asier
%A Moya-Rull, Daniel
%A Vilas-Zornoza, Amaia
%A Tarantino, Carolina
%A Romero, Juan Pablo
%A Jonsson, Gustav
%A Oria, Roger
%A Leopoldi, Alexandra
%A Hagelkruys, Astrid
%A Gallo, Maria
%A González, Federico
%A Domingo-Pedrol, Pere
%A Gavaldà, Aleix
%A Del Pozo, Carmen Hurtado
%A Hasan Ali, Omar
%A Ventura-Aguiar, Pedro
%A Campistol, Josep María
%A Prosper, Felipe
%A Mirazimi, Ali
%A Boulant, Steeve
%A Penninger, Josef M
%A Montserrat, Nuria
%T A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
%J Cell metabolism
%V 34
%N 6
%@ 1550-4131
%C Cambridge, Mass.
%I Cell Press
%M DKFZ-2022-01246
%P 857 - 873.e9
%D 2022
%X 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.
%K Angiotensin-Converting Enzyme 2
%K COVID-19
%K Diabetes Mellitus
%K Diabetic Nephropathies
%K Humans
%K Kidney: metabolism
%K Organoids
%K Peptidyl-Dipeptidase A: genetics
%K Peptidyl-Dipeptidase A: metabolism
%K SARS-CoV-2
%K ACE2 (Other)
%K COVID-19 (Other)
%K SARS-CoV-2 (Other)
%K angiotensin-converting enzyme 2 (Other)
%K diabetes 2 (Other)
%K human kidney organoids (Other)
%K Peptidyl-Dipeptidase A (NLM Chemicals)
%K Angiotensin-Converting Enzyme 2 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35561674
%2 pmc:PMC9097013
%R 10.1016/j.cmet.2022.04.009
%U https://inrepo02.dkfz.de/record/180319