Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria

Sci Rep. 2018 Oct 3;8(1):14723. doi: 10.1038/s41598-018-33082-x.


Kidney-derived c-kit+ cells exhibit progenitor/stem cell properties and can regenerate epithelial tubular cells following ischemia-reperfusion injury in rats. We therefore investigated whether c-kit+ progenitor/stem cells contribute to podocyte repair in a rat model of acute proteinuria induced by puromycin aminonucleoside (PAN), the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. We found that c-kit+ progenitor/stem cells accelerated kidney recovery by improving foot process effacement (foot process width was lower in c-kit group vs saline treated animals, P = 0.03). In particular, these cells engrafted in small quantity into tubules, vessels, and glomeruli, where they occasionally differentiated into podocyte-like cells. This effect was related to an up regulation of α-Actinin-4 and mTORC2-Rictor pathway. Activation of autophagy by c-kit+ progenitor/stem cells also contributed to kidney regeneration and intracellular homeostasis (autophagosomes and autophagolysosomes number and LC3A/B-I and LC3A/B-II expression were higher in the c-kit group vs saline treated animals, P = 0.0031 and P = 0.0009, respectively). Taken together, our findings suggest that kidney-derived c-kit+ progenitor/stem cells exert reparative effects on glomerular disease processes through paracrine effects, to a lesser extent differentiation into podocyte-like cells and contribution to maintenance of podocyte cytoskeleton after injury. These findings have clinical implications for cell therapy of glomerular pathobiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / genetics
  • Animals
  • Cell Differentiation / genetics
  • Glomerulosclerosis, Focal Segmental / genetics
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Glomerulus / growth & development
  • Kidney Glomerulus / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 2 / genetics
  • Nephrosis, Lipoid
  • Podocytes / metabolism*
  • Proteinuria / chemically induced
  • Proteinuria / genetics*
  • Proteinuria / pathology
  • Proto-Oncogene Proteins c-kit / genetics*
  • Puromycin Aminonucleoside / toxicity
  • Rats
  • Regeneration / genetics*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / pathology
  • Stem Cells / metabolism


  • ACTN4 protein, human
  • Actinin
  • Puromycin Aminonucleoside
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • Mechanistic Target of Rapamycin Complex 2

Supplementary concepts

  • Segmental glomerulosclerosis