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SHR Neuro Cancer Cardio Lipid Metab Microb
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; Hasan, Ali, O; Ventura-Aguiar, P; Campistol, JM; Prosper, F; Mirazimi, A; Boulant, S; Penninger, JM; Montserrat, N.
A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
Cell Metab. 2022; 34(6): 857-873.e9.
Doi: 10.1016/j.cmet.2022.04.009
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- Co-authors Med Uni Graz
- Jonsson Gustav
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Angiotensin-Converting Enzyme 2 - metabolism
- COVID-19 - administration & dosage
- Diabetes Mellitus - administration & dosage
- Diabetic Nephropathies - administration & dosage
- Humans - administration & dosage
- Kidney - metabolism
- Organoids - administration & dosage
- Peptidyl-Dipeptidase A - genetics, metabolism
- SARS-CoV-2 - administration & dosage