Post-transcriptional regulation as a key driver of intrinsic kidney regeneration

The increasing prevalence of noncommunicable diseases such as diabetes and hypertension have caused an alarming increase in chronic kidney disease (CKD). Augmenting the capacity of the kidney to regenerate intrinsically is a major challenge that could prevent irreversible kidney failure. While the cells of the Renin-Lineage (CoRL) play a critical role in regulating blood pressure and fluid and electrolyte homeostasis, recently they were also found to be a niche of pluripotent progenitor cells that can replace injured kidney tissue. This newly discovered intrinsic mechanism of regeneration may provide a promising therapeutic target to prevent the development of CKD. We found evidence that microRNAs coordinate a post-transcriptional regulatory network that drives the regenerative phenotype of the CoRL. By implementing in vitro and in vivo approaches involving mouse models that allow fate-tracing of CoRL (and conditional knockout models as well as knockdown/overexpression strategies), I aim to demonstrate that modulation of posttranscriptional regulation can stimulate the regenerative capacity of the CoRL. Taken together, the regenerative switch of the CoRL provides the kidney with an elegant mechanism to translate impaired kidney function into a reparative response. Our studies aim to provide novel options to modulate the intrinsic regenerative capacity of the kidney for the development of innovative approaches to counteract CKD.