title: A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan; Department of Urology, Changzhou Second Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors: Li
authors: L
authors: Zuo
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Keiichi
authors: K
authors: Tozawa
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. Electronic address: a-okada@med.nagoya-cu.ac.jp.
authors: Atsushi
authors: A
authors: Okada
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Takahiro
authors: T
authors: Yasui
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Kazumi
authors: K
authors: Taguchi
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Yasuhiko
authors: Y
authors: Ito
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Yasuhiko
authors: Y
authors: Hirose
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Yasuhiro
authors: Y
authors: Fujii
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Kazuhiro
authors: K
authors: Niimi
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Shuzo
authors: S
authors: Hamamoto
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Ryosuke
authors: R
authors: Ando
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Yasunori
authors: Y
authors: Itoh
authors: Department of Urology, Changzhou Second Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors: Jiangang
authors: J
authors: Zou
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors: Kenjiro
authors: K
authors: Kohri
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007669:Kidney Calculi / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D051379:Mice
chemical_list: D016207:Cytokines; D002129:Calcium Oxalate
keywords: inflammation; kidney; metabolic syndrome X; obesity; urolithiasis