{"id":73521,"date":"2024-05-15T16:46:01","date_gmt":"2024-05-15T14:46:01","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=73521"},"modified":"2025-12-05T17:20:08","modified_gmt":"2025-12-05T16:20:08","slug":"glomerular-endothelial-cell-senescence-drives-age-related-kidney-disease-through-pai-1","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/glomerular-endothelial-cell-senescence-drives-age-related-kidney-disease-through-pai-1\/","title":{"rendered":"Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-73521","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"EMBO Mol Med.","date_de_publication":"20211108","numero_doi":"10.15252\/emmm.202114146","equipe":[262],"auteurs-liste":[{"texte_libre":false,"auteur-lien":71595,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Oc\u00e9ane Le Goff"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Fr\u00e9d\u00e9ric Soysouvanh"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Florence Vasseur"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Marine Tanou"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Cl\u00e9ment Nguyen"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Lucile Amrouche"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Julien Le Guen"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Oriana Saltel-Fulero"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Tanguy Meunier"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Thao Nguyen-Khoa"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Marion Rabant"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Dominique Nochy"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Christophe Legendre"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"G\u00e9rard Friedlander"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Bennett G Childs"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Daren J Baker"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Bertrand Knebelmann"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Dany Anglicheau"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Fabien Milliat"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Fabiola Terzi"}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/34725920\/"}],"paragraphe":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross-talk between senescent endothelial cells and podocytes, through PAI-1. In vivo, selective inactivation of PAI-1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI-1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK-ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI-1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI-1 was associated with age-related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI-1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.<\/p>\r\n<\/div>","paragraphe_en":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross-talk between senescent endothelial cells and podocytes, through PAI-1. In vivo, selective inactivation of PAI-1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI-1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK-ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI-1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI-1 was associated with age-related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI-1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.<\/p>\r\n<\/div>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1 - CRI<\/title>\n<meta name=\"robots\" content=\"noindex, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1 - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/glomerular-endothelial-cell-senescence-drives-age-related-kidney-disease-through-pai-1\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-12-05T16:20:08+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/glomerular-endothelial-cell-senescence-drives-age-related-kidney-disease-through-pai-1\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/glomerular-endothelial-cell-senescence-drives-age-related-kidney-disease-through-pai-1\/\",\"name\":\"Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1 - 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