講演・口頭発表等

2020年10月22日

Am80, a Synthetic Retinoic Acid Receptor α-Specific Agonist, Suppresses Peritoneal Fibrosis via Inhibition of Krüppel-Like Transcription Factor 5 in Mice

Kidney Week 2020
  • Kumiko Muta
  • ,
  • Yuka Nakazawa
  • ,
  • Yoko Obata
  • ,
  • Hiro Inoue
  • ,
  • Kenta Torigoe
  • ,
  • Kazuo Yamamoto
  • ,
  • Tomoya Nishino

記述言語
英語
会議種別
ポスター発表

BACKGROUND
We presented previously that Am80, a synthetic retinoic acid receptor a specific agonist, inhibited the expression of Krüppel-like transcription factor 5 (KLF5) and reduced peritoneal fibrosis in mice. Now, we examined further detail about the mechanism to inhibit peritoneal fibrosis.

METHODS
Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. After 3 weeks of treatment, peritoneal tissues were examined using serial sections by immunohistochemistry to identify what kind of cells expressed KLF5. Am80 was given in mouse fibroblasts stimulated by transforming growth factor β1 (TGF-β1) and the expression of KLF5 was assessed by Western blotting.

RESULTS
While KLF5 was expressed in the thickened submesothelial area of CG injected mice, Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening. The numbers of TGFβ positive cells, a-smooth muscle actin (aSMA) or F4/80 positive cells were significantly decreased in Am80 treated group. KLF5 was expressed in aSMA, F4/80 or CD31 positive cells. Western blotting for KLF5 showed the tendency that KLF5 expression was decreased in higher concentration of Am80 in mouse fibroblasts stimulated by TGF-β1 in vitro.

CONCLUSION
These results indicate the KLF5 might not only associate phenotypical differentiation from fibroblasts to myofibroblasts but also regulate inflammatory responses and angiogenesis in peritoneal fibrosis model. Am80 can suppress peritoneal fibrosis through inhibiting these mechanisms.