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https://observatorio.fm.usp.br/handle/OPI/29679
Title: | Kidney-derived c-kit(+) progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria |
Authors: | RANGEL, Erika B.; GOMES, Samirah A.; KANASHIRO-TAKEUCHI, Rosemeire; SALTZMAN, Russell G.; WEI, Changli; RUIZ, Phillip; REISER, Jochen; HARE, Joshua M. |
Citation: | SCIENTIFIC REPORTS, v.8, article ID 14723, 17p, 2018 |
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 alpha-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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/29 |
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art_RANGEL_Kidneyderived_ckit_progenitorstem_cells_contribute_to_podocyte_recovery_2018.PDF | publishedVersion (English) | 3 MB | Adobe PDF | View/Open |
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