M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development

Taguchi, Kazumi; Okada, Atsushi; Hamamoto, Shuzo; Unno, Rei; Moritoki, Yoshinobu; Ando, Ryosuke; Mizuno, Kentaro; Tozawa, Keiichi; Kohri, Kenjiro; Yasui, Takahiro

doi:10.1038/srep35167

Cited by 80 publications

(99 citation statements)

References 59 publications

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“…A study reported that Th1 cells drove the pro‐inflammatory and Th2 the anti‐inflammatory response in atherosclerosis, which has similar calcification lesions on the vascular endothelial cells as urolithiasis . Interestingly, the pro‐inflammatory/Th1 phenotype is reportedly predominant in renal mesangial cells and tubular epithelial cells under diabetic nephropathy, which is in line with the results of our previous studies showing that the renal tissues of kidney stone patients and crystal‐forming mice shifted towards pro‐inflammatory and M1 macrophage phenotypes. In the present study, both the Th1‐ and Th2‐related pathways were upregulated in RP‐containing tissues of CaP SFs; however, validation of the expressions of these genes using PCR could not distinguish the tendency of either the Th1 or Th2 polarization between the papillary tissues of CaOx SFs and CaP SFs.…”

Section: Discussionsupporting

confidence: 89%

Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

et al. 2019

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Objectives To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones. Methods Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out. Results Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque‐containing tissues of calcium phosphate stone‐forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque‐containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression. Conclusions The present results show the upregulation of helper T‐cell signaling pathways in Randall's plaque‐containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T‐cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.

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Section: Discussionsupporting

confidence: 89%

Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

et al. 2019

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“…32 However, activated macrophages have two major forms: the classically activated form (M1), which facilitates crystal formation and worsens the renal condition, and the alternatively activated form (M2), which suppresses crystal formation and exerts anti-inflammatory and tissue healing effects. 32 Furthermore, a recent study has suggested that CaOx promotes monocyte/macrophage differentiation into M1-like macrophages. In summary, as the main chemokine for monocytes and the initial cytokines in the inflammatory cascade, MCP-1 plays a vital role in CaOx stone formation.…”

Section: Mcp-1 Expression Shows a Positive Association With Hoxa11-mentioning

confidence: 99%

LncRNA HOXA11‐AS regulates calcium oxalate crystal–induced renal inflammation via miR‐124‐3p/MCP‐1

Yan

Zhang

et al. 2019

J Cellular Molecular Medi

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Long noncoding RNA (lncRNA) has been suggested to play an important role in a variety of diseases over the past decade. In a previous study, we identified a novel lncRNA, termed HOXA11‐AS, which was significantly up‐regulated in calcium oxalate (CaOx) nephrolithiasis. However, the biological function of HOXA11‐AS in CaOx nephrolithiasis remains poorly defined. Here, we demonstrated that HOXA11‐AS was significantly up‐regulated in CaOx nephrolithiasis both in vivo and in vitro. Gain‐/loss‐of‐function studies revealed that HOXA11‐AS inhibited proliferation, promoted apoptosis and aggravated cellular damage in HK‐2 cells exposed to calcium oxalate monohydrate (COM). Further investigations showed that HOXA11‐AS regulated monocyte chemotactic protein 1 (MCP‐1) expression in HK‐2 cell model of CaOx nephrolithiasis. In addition, online bioinformatics analysis and dual‐luciferase reporter assay results showed that miR‐124‐3p directly bound to HOXA11‐AS and the 3'UTR of MCP‐1. Furthermore, rescue experiment results revealed that HOXA11‐AS functioned as a competing endogenous RNA to regulate MCP‐1 expression through sponging miR‐124‐3p and that overexpression of miR‐124‐3p restored the inhibitory effect of proliferation, promotion effects of apoptosis and cell damage induced by HOXA11‐AS overexpression. Taken together, HOXA11‐AS mediated CaOx crystal–induced renal inflammation via the miR‐124‐3p/MCP‐1 axis, and this outcome may provide a good potential therapeutic target for nephrolithiasis.

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“…Monocytes and macrophages have been implicated in CaOx stone disease in both humans and rodent models ( 13 – 16 ). Hyperoxaluric C57BL/6J mice expressed M-CSF and CCL2 which could potentially recruit monocytes ( 14 ); hyperoxaluric C57BL/6J mice that received M1 macrophage transfusions displayed increased CaOx production of IL-6 and TNFα compared to those that received M2 macrophage transfusions ( 15 ). In addition, M-CSF-deficient mice had significantly higher CaOx deposition in the kidneys than those of the wild-type mice ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages

et al. 2018

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PurposeA number of hyperoxaluric states have been associated with calcium oxalate (CaOx) deposits in the kidneys. In animal models of stone disease, these crystals interact with circulating monocytes that have migrated into the kidney as part of innate immunity. Similarly, macrophages surround CaOx crystals in kidneys of patients excreting high levels of oxalate. We investigate the effect of this exposure and subsequent human immunological response in vitro.Materials and methodsPrimary human monocytes were collected from healthy donors and exposed to CaOx, potassium oxalate, and zinc oxalate (ZnOx). Cytokine production was measured with a multiplex ELISA. Quantitative reverse transcription-polymerase chain reaction was done to validate the mRNA profile expression. M1 macrophage phenotype was confirmed with immunofluorescence microscopy.ResultsBoth primary monocytes and THP-1 cells, a human monocytic cell line, respond strongly to CaOx crystals in a dose-dependent manner producing TNF-α, IL-1β, IL-8, and IL-10 transcripts. Exposure to CaOx followed by 1 h with LPS had an additive effect for cytokine production compared to LPS alone, however, LPS followed by CaOx led to significant decrease in cytokine production. Supernatants taken from monocytes were previously exposed to CaOx crystals enhance M2 macrophage crystal phagocytosis. CaOx, but not potassium or ZnOx, promotes monocyte differentiation into inflammatory M1-like macrophages.ConclusionIn our in vitro experiment, human monocytes were activated by CaOx and produced inflammatory cytokines. Monocytes recognized CaOx crystals through a specific mechanism that can enhance or decrease the innate immune response to LPS. CaOx promoted M1 macrophage development. These results suggest that monocytes have an important role promoting CaOx-induced inflammation.

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M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development

Cited by 80 publications

References 59 publications

Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

LncRNA HOXA11‐AS regulates calcium oxalate crystal–induced renal inflammation via miR‐124‐3p/MCP‐1

Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages

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