1. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment
- Author
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Kazuhiro Niimi, Li Zuo, Jian-Gang Zou, Ryosuke Ando, Kenjiro Kohri, Kazumi Taguchi, Yasunori Itoh, Keiichi Tozawa, Atsushi Okada, Yasuhiro Fujii, Yasuhiko Ito, Yasuhiko Hirose, Takahiro Yasui, and Shuzo Hamamoto
- Subjects
medicine.medical_specialty ,Urology ,Cell ,Inflammation ,Enzyme-Linked Immunosorbent Assay ,Kidney Calculi ,Mice ,Internal medicine ,3T3-L1 Cells ,medicine ,Adipocytes ,Animals ,Osteopontin ,Interleukin 6 ,Metabolic Syndrome ,Kidney ,biology ,Adiponectin ,Calcium Oxalate ,Macrophages ,Cell biology ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,Kidney Tubules ,biology.protein ,Cytokines ,medicine.symptom ,Fetal bovine serum - Abstract
We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation.Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells.Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types.
- Published
- 2014