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- Title
Increased crystal-cell interaction in vitro under co-culture of renal tubular cells and adipocytes by in vitro co-culture paracrine systems simulating metabolic syndrome.
- Authors
Ichikawa, Jun; Okada, Atsushi; Taguchi, Kazumi; Fujii, Yasuhiro; Zuo, Li; Niimi, Kazuhiro; Hamamoto, Shuzo; Kubota, Yasue; Umemoto, Yukihiro; Itoh, Yasunori; Yasui, Takahiro; Kawai, Noriyasu; Tozawa, Keiichi; Kohri, Kenjiro
- Abstract
We established an experimental co-culture system for renal tubular cells and adipocytes to investigate kidney stone formation mechanisms under metabolic syndrome (MetS) conditions and examined the interaction between these cells morphologically and genetically. M-1s and 3T3-L1s were cultured individually (control, CON), with 24-h culture media from each cell type added to the other cell type (replacement, RP) in 2-layer co-culture dishes for 24 h (transwell, TW). M-1s were then exposed to calcium oxalate monohydrate (COM) crystals, and attached C-labeled COM crystals were quantified. Expression of kidney stone- and adipocyte-related genes was analyzed. The radioactivity of adherent COM crystals significantly increased in TW and was relatively higher in RP compared to CON. M-1s demonstrated significant upregulation of adiponectin ( Adipoq) in RP and secreted phosphoprotein 1 ( Spp1) in TW compared to CON before COM crystal exposure, and significant downregulation of Spp1 in TW and upregulation of tumor necrosis factor ( Tnf), interleukin 6 ( Il- 6), and chemokine (C-C motif) ligand 2 ( Ccl2) compared to CON after COM crystal exposure. 3T3-L1s showed significant upregulation of Spp1, Adipoq, Tnf- α, and Ccl2 compared to CON. Enzyme-linked immunosorbent assays of co-culture medium revealed significantly increased TNF-α in TW. Our results highlight the potential for paracrine interactions between renal tubular cells and adipocytes and suggest that MetS conditions may lead to kidney stone formation.
- Subjects
OSTEOPONTIN; PARACRINE mechanisms; METABOLIC syndrome; KIDNEY stones; CALCIUM oxalate; TUMOR necrosis factors; INTERLEUKIN-6
- Publication
Urolithiasis, 2014, Vol 42, Issue 1, p17
- ISSN
2194-7228
- Publication type
Article
- DOI
10.1007/s00240-013-0612-5