論文

査読有り 国際誌
2020年

High-mobility group box 1 fragment suppresses adverse post-infarction remodeling by recruiting PDGFRα-positive bone marrow cells.

PloS one
  • Takasumi Goto
  • ,
  • Shigeru Miyagawa
  • ,
  • Katsuto Tamai
  • ,
  • Ryohei Matsuura
  • ,
  • Takashi Kido
  • ,
  • Toru Kuratani
  • ,
  • Kazuo Shimamura
  • ,
  • Ryoto Sakaniwa
  • ,
  • Akima Harada
  • ,
  • Yoshiki Sawa

15
4
開始ページ
e0230392
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0230392

OBJECTIVES: High-mobility group box 1 protein (HMGB1) fragment enhances bone marrow-derived mesenchymal stem cell (BM-MSC) recruitment to damaged tissue to promote tissue regeneration. This study aimed to evaluate whether systemic injection of HMGB1 fragment could promote tissue repair in a rat model of myocardial infarction (MI). METHODS: HMGB1 (n = 14) or phosphate buffered saline (n = 12, control) was administered to MI rats for 4 days. Cardiac performance and left ventricular remodeling were evaluated using ultrasonography and immunostaining. BM-MSC recruitment to damaged tissue in green fluorescent protein-bone marrow transplantation (GFP-BMT) models was evaluated using immunostaining. RESULTS: At four weeks post-treatment, the left ventricular ejection fraction was significantly improved in the HMGB1 group compared to that in the control. Interstitial fibrosis and cardiomyocyte hypertrophy were also significantly attenuated in the HMGB1 group compared to the control. In the peri-infarction area, VEGF-A mRNA expression was significantly higher and TGFβ expression was significantly attenuated in the HMGB1 group than in the control. In GFP-BMT rats, GFP+/PDGFRα+ cells were significantly mobilized to the peri-infarction area in the HMGB1 group compared to that in the control, leading to the formation of new vasculature. In addition, intravital imaging revealed that more GFP+/PDGFRα+ cells were recruited to the peri-infarction area in the HMGB1 group than in the control 12 h after treatment. CONCLUSIONS: Systemic administration of HMGB1 induced angiogenesis and reduced fibrosis by recruiting PDGFRα+ mesenchymal cells from the bone marrow, suggesting that HMGB1 administration might be a new therapeutic approach for heart failure after MI.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0230392
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32275672
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147742

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