Abstract
Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-like receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single-cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.
Highlights
Mechanisms of endogenous regeneration and repair have been proposed for several mammalian organs [1]
Using chemical and genetic inhibitors, we demonstrated that Rho kinase (ROCK) activity is required to mediate the effects of stiffness on renal progenitor proliferation, migration and differentiation [35]
The mechanisms underlying this process was further delineated in a follow-up paper, where they showed that a dual treatment of leptin-deficient ob/ob mice with a selective antagonist of the endothelin-1 type A receptor (ETAR) in combination with RAAS inhibition led to an improved phenotype [40], characterized by the activation of parietal epithelial cells (PECs) and increased number of podocytes
Summary
Mechanisms of endogenous regeneration and repair have been proposed for several mammalian organs [1]. Immature ones endowed with twice as many Pax2+ progenitors per glomerular podocyte count in cells expressing the neural cell adhesion molecule (NCAM) and the progenitor cell marker healthy conditions [12]. The specific genetic tracking of progenitors among PECs demonstrated their involvement in the generation of hyperplastic glomerular lesions that could be envisioned as a failure to regenerate podocyte following injury [4]. From all these studies, it is clear that renal progenitors localized among. Knowing the mechanisms that drive a correct proliferative and differentiative response of renal progenitors during homeostasis and following injury is of crucial importance and may allow the identification of putative modulators to boost the regenerative potential of renal progenitors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
