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A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
Garreta, Elena; Prado, Patricia; Stanifer, Megan L; Monteil, Vanessa; Marco, Andrés; Ullate-Agote, Asier; Moya-Rull, Daniel; Vilas-Zornoza, Amaia; Tarantino, Carolina; Romero, Juan Pablo; Jonsson, Gustav; Oria, Roger; Leopoldi, Alexandra; Hagelkruys, Astrid; Gallo, Maria; González, Federico; Domingo-Pedrol, Pere; Gavaldà, Aleix; Del Pozo, Carmen Hurtado; Hasan Ali, Omar; Ventura-Aguiar, Pedro; Campistol, Josep María; Prosper, Felipe; Mirazimi, Ali; Boulant, Steeve; Penninger, Josef M; Montserrat, Nuria.
  • Garreta E; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Prado P; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Stanifer ML; Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany; Research Group "Cellular Polarity and Viral Infection," German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Molecular Genetics and Microbiology, College of Medicine, Unive
  • Monteil V; Karolinska Institute and Karolinska University Hospital, Unit of Clinical Microbiology, 17182 Stockholm, Sweden.
  • Marco A; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Ullate-Agote A; Área de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Univers
  • Moya-Rull D; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Vilas-Zornoza A; Área de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Univers
  • Tarantino C; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Romero JP; Área de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain.
  • Jonsson G; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
  • Oria R; Center for Bioengineering and Tissue Regeneration, UCSF, San Francisco, CA, USA.
  • Leopoldi A; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
  • Hagelkruys A; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
  • Gallo M; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • González F; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Domingo-Pedrol P; Internal Medicine Department, Hospital Universitario de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Gavaldà A; Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
  • Del Pozo CH; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Hasan Ali O; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • Ventura-Aguiar P; Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
  • Campistol JM; Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
  • Prosper F; Área de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Univers
  • Mirazimi A; Karolinska Institute and Karolinska University Hospital, Unit of Clinical Microbiology, 17182 Stockholm, Sweden; National Veterinary Institute, Uppsala, Sweden. Electronic address: ali.mirazimi@ki.se.
  • Boulant S; Research Group "Cellular Polarity and Viral Infection," German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Infectious Diseases, Virology, Heidelberg University H
  • Penninger JM; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: josef.penninger@ubc.ca.
  • Montserrat N; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingenierí
Cell Metab ; 34(6): 857-873.e9, 2022 06 07.
Article in English | MEDLINE | ID: covidwho-1926324
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Nephropathies / Angiotensin-Converting Enzyme 2 / COVID-19 Limits: Humans Language: English Journal: Cell Metab Journal subject: Metabolism Year: 2022 Document Type: Article Affiliation country: J.cmet.2022.04.009

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Nephropathies / Angiotensin-Converting Enzyme 2 / COVID-19 Limits: Humans Language: English Journal: Cell Metab Journal subject: Metabolism Year: 2022 Document Type: Article Affiliation country: J.cmet.2022.04.009