Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation
Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation
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DOI：
10.1681/asn.2013060675
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发表时间：
2014-08-01
影响因子：
13.6
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Taguchi, Kazumi;Okada, Atsushi;Kohri, Kenjiro
我们最近报道的证据表明，迁移性巨噬细胞（M φ s）消除高尿酸小鼠肾结晶。M phi可以是炎性的（M1）或抗炎的（M2），并且集落刺激因子-1（CSF-1）介导向M2M phi表型的极化。M2M phi s促进肾组织修复和再生，但尚不清楚这些细胞是否参与抑制肾晶体形成。我们使用缺乏M2 M φ s的CSF-1缺陷小鼠研究了M2 M φ s在高草酸尿期间肾结晶形成中的作用。与野生型小鼠相比，CSF-1缺陷小鼠肾脏草酸钙晶体沉积量显著增加。用重组人CSF-1治疗增加了M2相关基因的表达，并显着减少了CSF-1缺陷型和野生型小鼠的肾晶体数量。流式细胞术显示，CSF-1缺乏导致CD 11b（+）F4/80（+）CD 163（+）CD 206（hi）细胞数量减少，这些细胞代表M2样M phi。此外，将M2M phi输注到CSF-1缺陷小鼠中抑制了肾晶体沉积。体外一水草酸钙晶体吞噬试验显示，M2极化M phi s的晶体吞噬率高于M1极化M phi s或肾小管细胞。基因阵列分析表明，CSF-1缺陷导致M2和结石相关基因表达紊乱。总的来说，我们的研究结果提供了令人信服的证据，CSF-1信号在肾晶体形成的抑制作用。
We recently reported evidence suggesting that migrating macrophages (M phi s) eliminate renal crystals in hyperoxaluric mice. M phi s can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2M phi phenotype. M2M phi s promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2M phi s in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2M phi s. 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 M phi s showed that CSF-1 deficiency resulted in a smaller population of CD11b(+)F4/80(+)CD163(+)CD206(hi) cells, which represent M2-like M phi s. Additionally, transfusion of M2M phi s into CSF-1 deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized M phi s than M1-polarized M phi s 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.