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Stem Cell Reports. 2015 Aug 11;5(2):248-63. doi: 10.1016/j.stemcr.2015.07.003. Epub 2015 Jul 30.

Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced.

Author information

1
Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. Electronic address: laura.lasagni@unifi.it.
2
Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
3
Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; Department of Clinical and Experimental Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
4
Nephrology Unit, Meyer Children's University Hospital, Viale Pieraccini 24, 50141 Florence, Italy.
5
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
6
Department of Oncology and Children's Research Center, University Children's Hospital, Steinwiesenstrasse 75, 8032 Zurich, Switzerland.
7
Pathology Unit, Meyer Children's Hospital, Viale Pieraccini 24, 50141 Florence, Italy.
8
Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; Department of Clinical and Experimental Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; Nephrology Unit, Meyer Children's University Hospital, Viale Pieraccini 24, 50141 Florence, Italy. Electronic address: paola.romagnani@unifi.it.

Abstract

Podocyte loss is a general mechanism of glomerular dysfunction that initiates and drives the progression of chronic kidney disease, which affects 10% of the world population. Here, we evaluate whether the regenerative response to podocyte injury influences chronic kidney disease outcome. In models of focal segmental glomerulosclerosis performed in inducible transgenic mice where podocytes are tagged, remission or progression of disease was determined by the amount of regenerated podocytes. When the same model was established in inducible transgenic mice where renal progenitors are tagged, the disease remitted if renal progenitors successfully differentiated into podocytes, while it persisted if differentiation was ineffective, resulting in glomerulosclerosis. Treatment with BIO, a GSK3s inhibitor, significantly increased disease remission by enhancing renal progenitor sensitivity to the differentiation effect of endogenous retinoic acid. These results establish renal progenitors as critical determinants of glomerular disease outcome and a pharmacological enhancement of their differentiation as a possible therapeutic strategy.

PMID:
26235895
PMCID:
PMC4618832
DOI:
10.1016/j.stemcr.2015.07.003
[Indexed for MEDLINE]
Free PMC Article

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