TY - JOUR
T1 - Colony-stimulating factor-1 signaling suppresses renal crystal formation
AU - Taguchi, Kazumi
AU - Okada, Atsushi
AU - Kitamura, Hiroshi
AU - Yasui, Takahiro
AU - Naiki, Taku
AU - Hamamoto, Shuzo
AU - Ando, Ryosuke
AU - Mizuno, Kentaro
AU - Kawai, Noriyasu
AU - Tozawa, Keiichi
AU - Asano, Kenichi
AU - Tanaka, Masato
AU - Miyoshi, Ichiro
AU - Kohri, Kenjiro
N1 - Publisher Copyright:
Copyright © 2014 by the American Society of Nephrology.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - We recently reported evidence suggesting that migrating macrophages (Mws) eliminate renal crystals in hyperoxaluric mice. Mws can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mw phenotype. M2Mws promote renal tissue repair and regeneration, but it is not clearwhether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mws in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2Mws. Compared with wild-type mice, CSF-1-deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow cytometry of sorted renal Mws showed that CSF-1 deficiency resulted in a smaller population of CD11b+F4/80+CD163+CD206hi cells,which represent M2-like Mφs. Additionally, transfusion of M2Mφs intoCSF-1-deficientmice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mφs than M1-polarized Mws or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.
AB - We recently reported evidence suggesting that migrating macrophages (Mws) eliminate renal crystals in hyperoxaluric mice. Mws can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mw phenotype. M2Mws promote renal tissue repair and regeneration, but it is not clearwhether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mws in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2Mws. Compared with wild-type mice, CSF-1-deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow cytometry of sorted renal Mws showed that CSF-1 deficiency resulted in a smaller population of CD11b+F4/80+CD163+CD206hi cells,which represent M2-like Mφs. Additionally, transfusion of M2Mφs intoCSF-1-deficientmice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mφs than M1-polarized Mws or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.
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U2 - 10.1681/ASN.2013060675
DO - 10.1681/ASN.2013060675
M3 - Article
C2 - 24578130
AN - SCOPUS:84921686119
VL - 25
SP - 1680
EP - 1697
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 8
ER -