Colony-stimulating factor-1 signaling suppresses renal crystal formation

Kazumi Taguchi, Atsushi Okada, Hiroshi Kitamura, Takahiro Yasui, Taku Naiki, Shuzo Hamamoto, Ryosuke Ando, Kentaro Mizuno, Noriyasu Kawai, Keiichi Tozawa, Kenichi Asano, Masato Tanaka, Ichiro Miyoshi, Kenjiro Kohri

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35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1680-1697
Number of pages18
JournalJournal of the American Society of Nephrology
Volume25
Issue number8
DOIs
Publication statusPublished - 2014 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Taguchi, K., Okada, A., Kitamura, H., Yasui, T., Naiki, T., Hamamoto, S., Ando, R., Mizuno, K., Kawai, N., Tozawa, K., Asano, K., Tanaka, M., Miyoshi, I., & Kohri, K. (2014). Colony-stimulating factor-1 signaling suppresses renal crystal formation. Journal of the American Society of Nephrology, 25(8), 1680-1697. https://doi.org/10.1681/ASN.2013060675