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Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease
Remission and Can Be Pharmacologically Enhanced
#MMPMID26235895
Lasagni L
; Angelotti ML
; Ronconi E
; Lombardi D
; Nardi S
; Peired A
; Becherucci F
; Mazzinghi B
; Sisti A
; Romoli S
; Burger A
; Schaefer B
; Buccoliero A
; Lazzeri E
; Romagnani P
Stem Cell Reports
2015[Aug]; 5
(2
): 248-63
PMID26235895
show ga
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.
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