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@ARTICLE{Garreta:180319,
author = {E. Garreta and P. Prado and M. L. Stanifer$^*$ and V.
Monteil and A. Marco and A. Ullate-Agote and D. Moya-Rull
and A. Vilas-Zornoza and C. Tarantino and J. P. Romero and
G. Jonsson and R. Oria and A. Leopoldi and A. Hagelkruys and
M. Gallo and F. González and P. Domingo-Pedrol and A.
Gavaldà and C. H. Del Pozo and O. Hasan Ali and P.
Ventura-Aguiar and J. M. Campistol and F. Prosper and A.
Mirazimi and S. Boulant$^*$ and J. M. Penninger and N.
Montserrat},
title = {{A} diabetic milieu increases {ACE}2 expression and
cellular susceptibility to {SARS}-{C}o{V}-2 infections in
human kidney organoids and patient cells.},
journal = {Cell metabolism},
volume = {34},
number = {6},
issn = {1550-4131},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2022-01246},
pages = {857 - 873.e9},
year = {2022},
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.},
keywords = {Angiotensin-Converting Enzyme 2 / COVID-19 / Diabetes
Mellitus / Diabetic Nephropathies / Humans / Kidney:
metabolism / Organoids / Peptidyl-Dipeptidase A: genetics /
Peptidyl-Dipeptidase A: metabolism / SARS-CoV-2 / ACE2
(Other) / COVID-19 (Other) / SARS-CoV-2 (Other) /
angiotensin-converting enzyme 2 (Other) / diabetes 2 (Other)
/ human kidney organoids (Other) / Peptidyl-Dipeptidase A
(NLM Chemicals) / Angiotensin-Converting Enzyme 2 (NLM
Chemicals)},
cin = {F140},
ddc = {570},
cid = {I:(DE-He78)F140-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35561674},
pmc = {pmc:PMC9097013},
doi = {10.1016/j.cmet.2022.04.009},
url = {https://inrepo02.dkfz.de/record/180319},
}