TY  - JOUR
AU  - Garreta, Elena
AU  - Prado, Patricia
AU  - Stanifer, Megan L
AU  - Monteil, Vanessa
AU  - Marco, Andrés
AU  - Ullate-Agote, Asier
AU  - Moya-Rull, Daniel
AU  - Vilas-Zornoza, Amaia
AU  - Tarantino, Carolina
AU  - Romero, Juan Pablo
AU  - Jonsson, Gustav
AU  - Oria, Roger
AU  - Leopoldi, Alexandra
AU  - Hagelkruys, Astrid
AU  - Gallo, Maria
AU  - González, Federico
AU  - Domingo-Pedrol, Pere
AU  - Gavaldà, Aleix
AU  - Del Pozo, Carmen Hurtado
AU  - Hasan Ali, Omar
AU  - Ventura-Aguiar, Pedro
AU  - Campistol, Josep María
AU  - Prosper, Felipe
AU  - Mirazimi, Ali
AU  - Boulant, Steeve
AU  - Penninger, Josef M
AU  - Montserrat, Nuria
TI  - A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
JO  - Cell metabolism
VL  - 34
IS  - 6
SN  - 1550-4131
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2022-01246
SP  - 857 - 873.e9
PY  - 2022
AB  - 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.
KW  - Angiotensin-Converting Enzyme 2
KW  - COVID-19
KW  - Diabetes Mellitus
KW  - Diabetic Nephropathies
KW  - Humans
KW  - Kidney: metabolism
KW  - Organoids
KW  - Peptidyl-Dipeptidase A: genetics
KW  - Peptidyl-Dipeptidase A: metabolism
KW  - SARS-CoV-2
KW  - ACE2 (Other)
KW  - COVID-19 (Other)
KW  - SARS-CoV-2 (Other)
KW  - angiotensin-converting enzyme 2 (Other)
KW  - diabetes 2 (Other)
KW  - human kidney organoids (Other)
KW  - Peptidyl-Dipeptidase A (NLM Chemicals)
KW  - Angiotensin-Converting Enzyme 2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35561674
C2  - pmc:PMC9097013
DO  - DOI:10.1016/j.cmet.2022.04.009
UR  - https://inrepo02.dkfz.de/record/180319
ER  -