Detalle Publicación

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

Autores: Garreta, E.; Prado, P.; Stanifer, M. L.; Monteil, V.; Marco, A.; Ullate Agote, Asier; Moya-Rull, D.; Vilas Zornoza, Amaia; Tarantino, C.; Romero Riojas, Juan Pablo; Jonsson, G.; Oria, R.; Leopoldi, A.; Hagelkruys, A.; Gallo, M.; González, F.; Domingo-Pedrol, P.; Gavalda, A.; Hurtado del Pozo, C.; Hasan Ali, O.; Ventura-Aguiar, P.; Campistol, J. M.; Prosper Cardoso, Felipe; Mirazimi, A. (Autor de correspondencia); Boulant, S. (Autor de correspondencia); Penninger, J. M. (Autor de correspondencia); Montserrat, N. (Autor de correspondencia)
Título de la revista: CELL METABOLISM
ISSN: 1550-4131
Volumen: 34
Número: 6
Páginas: 857 - 873.e9
Fecha de publicación: 2022
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.