Characterization of vitamin A-storing cells in mouse fibrous kidneys using Cygb/STAP as a marker of activated stellate cells

  • Kida Yujiro
    Department of Anatomy II, School of Dental Medicine, Tsurumi University Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University
  • Asahina Kinji
    Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University
  • Inoue Kouji
    Research Center of Electron Microscopy, School of Dental Medicine, Tsurumi University
  • Kawada Norifumi
    Department of Hepatology, Graduate School of Medicine, Osaka City University
  • Yoshizato Katsutoshi
    Developmental Biology Laboratory, Department of Biological Science, Graduate School of Science, Hiroshima University
  • Wake Kenjiro
    Department of Anatomy II, School of Dental Medicine, Tsurumi University Liver Research Unit, Minophagen Pharmaceutical Co. Ltd.
  • Sato Tetsuji
    Department of Anatomy II, School of Dental Medicine, Tsurumi University Research Center of Electron Microscopy, School of Dental Medicine, Tsurumi University

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The expression of the cytoglobin/stellate cell activation-associated protein (Cygb/STAP) was recently confirmed in all splanchnic vitamin A-storing cells - including hepatic stellate cells (HSCs) - in normal conditions. In the hepatic fibrous lesion, the expression of Cygb/STAP has been shown to be upregulated in activated HSCs and myofibroblasts (MFs), which have synthesized extracellular matrices. Furthermore, splanchnic vitamin A-storing cells have been reported to be distributed in the kidney. In this study, we clarify the contribution of vitamin A-storing cells to renal fibrosis by focusing on Cygb/ STAP. Adult mice were subjected to unilateral ureteral obstruction (UUO) and kidneys were harvested 1, 3, 7, and 10 days after UUO.<BR> Numbers of Cygb/STAP-immunopositive cells as well as Cygb/STAP mRNA 3 days after UUO (UUO day 3 kidney) increased. Vitamin A-autofluorescence was observed in intertubular spaces of controls but gradually declined in a time-dependent manner after UUO. Cygb/STAP+ cells were not completely identical with α-smooth muscle actin (αSMA)-positive cells in the control or UUO day 7 kidneys. Immunohistochemical analysis for Cygb/STAP and fibulin-2 (Fib), a specific marker for distinguishing MFs from activated HSCs, revealed that the number of Fib+STAP+ cells (MFs) and Fib-STAP+ cells (splanchnic vitamin A-storing cells) significantly increased in UUO day 3 and UUO day 7 kidneys compared with the controls. Our present findings support the concept that Cygb/STAP can be a unique marker for splanchnic fibroblast-like cells, namely the vitamin A-storing cell lineage, and suggest that splanchnic vitamin A-storing cells contribute to renal fibrogenesis in the obstructed kidney.

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