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

Erika B. Rangel, Samirah A. Gomes, Rosemeire Takeuchi, Russell G. Saltzman, Changli Wei, Phillip Ruiz, Jochen Reiser, Joshua Hare

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number14723
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Podocytes
Proteinuria
Stem Cells
Kidney
Foot
Puromycin Aminonucleoside
Lipoid Nephrosis
Actinin
Focal Segmental Glomerulosclerosis
Autophagy
Cell- and Tissue-Based Therapy
Reperfusion Injury
Cytoskeleton
Regeneration
Homeostasis
Up-Regulation
Epithelial Cells
Maintenance

ASJC Scopus subject areas

  • General

Cite this

Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria. / Rangel, Erika B.; Gomes, Samirah A.; Takeuchi, Rosemeire; Saltzman, Russell G.; Wei, Changli; Ruiz, Phillip; Reiser, Jochen; Hare, Joshua.

In: Scientific Reports, Vol. 8, No. 1, 14723, 01.12.2018.

Research output: Contribution to journalArticle

Rangel, Erika B. ; Gomes, Samirah A. ; Takeuchi, Rosemeire ; Saltzman, Russell G. ; Wei, Changli ; Ruiz, Phillip ; Reiser, Jochen ; Hare, Joshua. / Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{424a472110fc4a7c8ffa6a2331bb33f1,
title = "Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria",
abstract = "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.",
author = "Rangel, {Erika B.} and Gomes, {Samirah A.} and Rosemeire Takeuchi and Saltzman, {Russell G.} and Changli Wei and Phillip Ruiz and Jochen Reiser and Joshua Hare",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-33082-x",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Kidney-derived c-kit+ progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria

AU - Rangel, Erika B.

AU - Gomes, Samirah A.

AU - Takeuchi, Rosemeire

AU - Saltzman, Russell G.

AU - Wei, Changli

AU - Ruiz, Phillip

AU - Reiser, Jochen

AU - Hare, Joshua

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054294235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054294235&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-33082-x

DO - 10.1038/s41598-018-33082-x

M3 - Article

C2 - 30283057

AN - SCOPUS:85054294235

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14723

ER -