Polyploid tubular cells initiate a TGF-β1 controlled loop that sustains polyploidization and fibrosis after acute kidney injury.

ABSTRACT: Polyploidization of tubular cells (TC) is triggered by acute kidney injury (AKI) to allow survival in the early phase after AKI, but in the long run promotes fibrosis and AKI-chronic kidney disease (CKD) transition. The molecular mechanism governing the link between polyploid TC and kidney fibrosis remains to be clarified. In this study, we demonstrate that immediately after AKI, expression of cell cycle markers mostly identifies a population of DNA-damaged polyploid TC. Using transgenic mouse models and single-cell RNA sequencing we show that, unlike diploid TC, polyploid TC accumulate DNA damage and survive, eventually resting in the G1 phase of the cell cycle. In vivo and in vitro single-cell RNA sequencing along with sorting of polyploid TC shows that these cells acquire a profibrotic

SUBMITTER: De Chiara L 

PROVIDER: S-EPMC10635654 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature