by Keyword: distal tubule
Garreta, E, Prado, P, Stanifer, ML, Monteil, V, Marco, A, Ullate-Agote, A, Moya-Rull, D, Vilas-Zornoza, A, Tarantino, C, Romero, JP, Jonsson, G, Oria, R, Leopoldi, A, Hagelkruys, A, Gallo, M, González, F, Domingo-Pedrol, P, Gavaldà, A, del Pozo, CH, Ali, OH, Ventura-Aguiar, P, Campistol, JM, Prosper, F, Mirazimi, A, Boulant, S, Penninger, JM, Montserrat, N, (2022). A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells Cell Metabolism 34, 857-873 
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.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
JTD Keywords: complications, coronavirus, cultured-cells, disease, distal tubule, mouse, protein, reveals, spike, Ace2, Angiotensin-converting enzyme 2, Angiotensin-converting enzyme-2, Covid-19, Diabetes 2, Human kidney organoids, Sars-cov-2
