Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1

Camille Cohen, Océane Le Goff, Frédéric Soysouvanh, Florence Vasseur, Marine Tanou, Clément Nguyen, Lucile Amrouche, Julien Le Guen, Oriana Saltel-Fulero, Tanguy Meunier, Thao Nguyen-Khoa, Marion Rabant, Dominique Nochy, Christophe Legendre, Gérard Friedlander, Bennett G. Childs, Daren J. Baker, Bertrand Knebelmann, Dany Anglicheau, Fabien MilliatFabiola Terzi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere14146
JournalEMBO Molecular Medicine
Issue number11
StatePublished - Nov 8 2021


  • PAI-1
  • aging nephropathy
  • endothelial–podocyte cross-talk
  • kidney transplantation
  • senescence

ASJC Scopus subject areas

  • Molecular Medicine


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