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SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To stud...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709832/ https://www.ncbi.nlm.nih.gov/pubmed/35032430 http://dx.doi.org/10.1016/j.stem.2021.12.010 |
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author | Jansen, Jitske Reimer, Katharina C. Nagai, James S. Varghese, Finny S. Overheul, Gijs J. de Beer, Marit Roverts, Rona Daviran, Deniz Fermin, Liline A.S. Willemsen, Brigith Beukenboom, Marcel Djudjaj, Sonja von Stillfried, Saskia van Eijk, Larissa E. Mastik, Mirjam Bulthuis, Marian Dunnen, Wilfred den van Goor, Harry Hillebrands, Jan-Luuk Triana, Sergio H. Alexandrov, Theodore Timm, Marie-Cherelle van den Berge, Bartholomeus T. van den Broek, Martijn Nlandu, Quincy Heijnert, Joelle Bindels, Eric M.J. Hoogenboezem, Remco M. Mooren, Fieke Kuppe, Christoph Miesen, Pascal Grünberg, Katrien Ijzermans, Ties Steenbergen, Eric J. Czogalla, Jan Schreuder, Michiel F. Sommerdijk, Nico Akiva, Anat Boor, Peter Puelles, Victor G. Floege, Jürgen Huber, Tobias B. van Rij, Ronald P. Costa, Ivan G. Schneider, Rebekka K. Smeets, Bart Kramann, Rafael |
author_facet | Jansen, Jitske Reimer, Katharina C. Nagai, James S. Varghese, Finny S. Overheul, Gijs J. de Beer, Marit Roverts, Rona Daviran, Deniz Fermin, Liline A.S. Willemsen, Brigith Beukenboom, Marcel Djudjaj, Sonja von Stillfried, Saskia van Eijk, Larissa E. Mastik, Mirjam Bulthuis, Marian Dunnen, Wilfred den van Goor, Harry Hillebrands, Jan-Luuk Triana, Sergio H. Alexandrov, Theodore Timm, Marie-Cherelle van den Berge, Bartholomeus T. van den Broek, Martijn Nlandu, Quincy Heijnert, Joelle Bindels, Eric M.J. Hoogenboezem, Remco M. Mooren, Fieke Kuppe, Christoph Miesen, Pascal Grünberg, Katrien Ijzermans, Ties Steenbergen, Eric J. Czogalla, Jan Schreuder, Michiel F. Sommerdijk, Nico Akiva, Anat Boor, Peter Puelles, Victor G. Floege, Jürgen Huber, Tobias B. van Rij, Ronald P. Costa, Ivan G. Schneider, Rebekka K. Smeets, Bart Kramann, Rafael |
author_sort | Jansen, Jitske |
collection | PubMed |
description | Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID. |
format | Online Article Text |
id | pubmed-8709832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-87098322021-12-28 SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids Jansen, Jitske Reimer, Katharina C. Nagai, James S. Varghese, Finny S. Overheul, Gijs J. de Beer, Marit Roverts, Rona Daviran, Deniz Fermin, Liline A.S. Willemsen, Brigith Beukenboom, Marcel Djudjaj, Sonja von Stillfried, Saskia van Eijk, Larissa E. Mastik, Mirjam Bulthuis, Marian Dunnen, Wilfred den van Goor, Harry Hillebrands, Jan-Luuk Triana, Sergio H. Alexandrov, Theodore Timm, Marie-Cherelle van den Berge, Bartholomeus T. van den Broek, Martijn Nlandu, Quincy Heijnert, Joelle Bindels, Eric M.J. Hoogenboezem, Remco M. Mooren, Fieke Kuppe, Christoph Miesen, Pascal Grünberg, Katrien Ijzermans, Ties Steenbergen, Eric J. Czogalla, Jan Schreuder, Michiel F. Sommerdijk, Nico Akiva, Anat Boor, Peter Puelles, Victor G. Floege, Jürgen Huber, Tobias B. van Rij, Ronald P. Costa, Ivan G. Schneider, Rebekka K. Smeets, Bart Kramann, Rafael Cell Stem Cell Clinical and Translational Report Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID. Cell Press 2022-02-03 /pmc/articles/PMC8709832/ /pubmed/35032430 http://dx.doi.org/10.1016/j.stem.2021.12.010 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical and Translational Report Jansen, Jitske Reimer, Katharina C. Nagai, James S. Varghese, Finny S. Overheul, Gijs J. de Beer, Marit Roverts, Rona Daviran, Deniz Fermin, Liline A.S. Willemsen, Brigith Beukenboom, Marcel Djudjaj, Sonja von Stillfried, Saskia van Eijk, Larissa E. Mastik, Mirjam Bulthuis, Marian Dunnen, Wilfred den van Goor, Harry Hillebrands, Jan-Luuk Triana, Sergio H. Alexandrov, Theodore Timm, Marie-Cherelle van den Berge, Bartholomeus T. van den Broek, Martijn Nlandu, Quincy Heijnert, Joelle Bindels, Eric M.J. Hoogenboezem, Remco M. Mooren, Fieke Kuppe, Christoph Miesen, Pascal Grünberg, Katrien Ijzermans, Ties Steenbergen, Eric J. Czogalla, Jan Schreuder, Michiel F. Sommerdijk, Nico Akiva, Anat Boor, Peter Puelles, Victor G. Floege, Jürgen Huber, Tobias B. van Rij, Ronald P. Costa, Ivan G. Schneider, Rebekka K. Smeets, Bart Kramann, Rafael SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title | SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title_full | SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title_fullStr | SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title_full_unstemmed | SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title_short | SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids |
title_sort | sars-cov-2 infects the human kidney and drives fibrosis in kidney organoids |
topic | Clinical and Translational Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709832/ https://www.ncbi.nlm.nih.gov/pubmed/35032430 http://dx.doi.org/10.1016/j.stem.2021.12.010 |
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