論文

国際誌
2022年2月18日

PPARγ Agonist Attenuates Vocal Fold Fibrosis in Rats via Regulation of Macrophage Activation.

The American journal of pathology
  • Shinji Kaba
  • ,
  • Yoshitaka Kawai
  • ,
  • Yuki Tanigami
  • ,
  • Hiroe Ohnishi
  • ,
  • Tomoko Kita
  • ,
  • Masayoshi Yoshimatsu
  • ,
  • Koichi Omori
  • ,
  • Yo Kishimoto

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ajpath.2022.02.002

Macrophages aid in wound healing by changing their phenotype and can be a key driver of fibrosis. However, the contribution of macrophage phenotype to fibrosis following vocal fold injury remains unclear. Peroxisome proliferator-activated receptor-γ (PPARγ) is expressed mainly by macrophages during early wound healing and regulates the macrophage phenotype. This study aimed to evaluate the effects of pioglitazone, a PPARγ agonist, on the macrophage phenotype and fibrosis following vocal fold injury in rats. Pioglitazone was injected into the rats' vocal folds on days 1, 3, 5, and 7 after injury, and the vocal fold lamina propria was evaluated on days 4 and 56 after injury. Moreover, THP-1-derived macrophages were treated with pioglitazone, and the expression of pro-inflammatory cytokines under lipopolysaccharide/interferon-γ stimulation was analyzed. The results revealed that pioglitazone reduced the expression of Ccl2 both in vivo and in vitro. Furthermore, pioglitazone decreased the density of inducible nitric oxide synthase+ CD68+ macrophages and inhibited the expression of fibrosis-related factors on day 4 after injury. On day 56 after injury, pioglitazone inhibited fibrosis, tissue contracture, and hyaluronic acid loss in a PPARγ-dependent manner. These results indicate that PPARγ activation could inhibit accumulation of inflammatory macrophages and improve tissue repair. Considered together, these findings imply that inflammatory macrophages play a key role in vocal fold fibrosis.

リンク情報
DOI
https://doi.org/10.1016/j.ajpath.2022.02.002
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35189097
ID情報
  • DOI : 10.1016/j.ajpath.2022.02.002
  • PubMed ID : 35189097

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