Project Details
Projekt
Modulation of tubular cell transition to a regenerative phenotype in AKI - diagnostic and therapeutic implications
Subject Area
Nephrology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445703531
Acute tubular injury accounts for the most common intrinsic cause for acute kidney injury (AKI). The “scattered tubular cell” (STC) phenotype was discovered as a uniform reaction of tubule cells triggered by injury. Our group was the first to identify an inducible transgenic mouse specifically labeling STCs. Our aim is to validate the relevance and implication of STCs in the course of AKI and to identify markers for AKI progression and outcome. In our preliminary work we have established a protocol to isolate by FACsorting intact single proximal tubular cells after staining against a specific proximal tubular marker. mRNA from injured proximal tubule cells as well as in controls has been isolated at different time-points and transcriptional profiles of single proximal tubular cells (scRNA-seq) were successfully generated. To investigate the STC phenotype and to gain novel insight into the pathophysiology of regeneration and repair upon AKI and transition to CKD we will apply single cell RNA sequencing and proteomic analyses of the STCs using our transgenic PEC-rtTA mice. By this approach, we aim to identify markers of STCs reflecting the stage and the outcome of kidney injury. The molecular and clinical expertise of Stamellou will be complemented by the expertise of Jankowski in proteomics to characterize in detail the STC phenotype and its implication in tubular regeneration. In conclusion, our application proposes a promising and innovative approach to improve clinical practice and care for patients with acute kidney injury.
DFG Programme
Clinical Research Units
