{"id":397,"date":"2022-10-17T16:03:00","date_gmt":"2022-10-17T16:03:00","guid":{"rendered":"https:\/\/boulantlab.com\/?post_type=publications&#038;p=397"},"modified":"2022-10-26T16:05:29","modified_gmt":"2022-10-26T16:05:29","slug":"a-diabetic-milieu-increases-ace2-expression-and-cellular-susceptibility-to-sars-cov-2-infections-in-human-kidney-organoids-and-patient-cells","status":"publish","type":"publications","link":"https:\/\/boulantlab.com\/publications\/a-diabetic-milieu-increases-ace2-expression-and-cellular-susceptibility-to-sars-cov-2-infections-in-human-kidney-organoids-and-patient-cells\/","title":{"rendered":"A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells"},"content":{"rendered":"\n<p>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.<\/p>\n","protected":false},"featured_media":398,"template":"","_links":{"self":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications\/397"}],"collection":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/types\/publications"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media\/398"}],"wp:attachment":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media?parent=397"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}