Abstract
AbstractHomeostatic renal filtration relies on the integrity of podocytes, which function in glomerular filtration. These highly specialized cells are damaged in 90% of chronic kidney disease, representing the leading cause of end-stage renal failure. Although modest podocyte renewal has been documented in adult mice, the mechanisms regulating this process remain largely unknown and controversial. Using a mouse model of Adriamycin-induced nephropathy, we find that the recovery of filtration function requires up-regulation of the endogenous telomerase component TERT. Previous work has shown that transient overexpression of catalytically inactive TERT (i-TERTci mouse model) has an unexpected role in triggering dramatic podocyte proliferation and renewal. We therefore used this model to conduct specific and stochastic lineage-tracing strategies in combination with high throughput sequencing methods. These experiments provide evidence that TERT drives the activation and clonal expansion of podocyte progenitor cells. Our findings demonstrate that the adult kidney bears intrinsic regenerative capabilities involving the protein component of telomerase, paving the way for innovative research toward the development of chronic kidney disease therapeutics.
Funder
Ligue Nationale Contre le Cancer Région Provence Alpes Côte d'Azur Inserm/CNRS, ATIP-Avenir LabEx Signalife La Société Francophone de Néphrologie Dialyse et Transplantation, AMGEN
Fondation ARC pour la Recherche sur le Cancer
Inserm, AGEMED ANR, TELOPOST
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Developmental Biology,Biomedical Engineering,Medicine (miscellaneous)
Cited by
2 articles.
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