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

Authors :
Goto T
Miyagawa S
Tamai K
Matsuura R
Kido T
Kuratani T
Shimamura K
Sakaniwa R
Harada A
Sawa Y
Source :
PloS one [PLoS One] 2020 Apr 10; Vol. 15 (4), pp. e0230392. Date of Electronic Publication: 2020 Apr 10 (Print Publication: 2020).
Publication Year :
2020

Abstract

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).<br />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.<br />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.<br />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.<br />Competing Interests: The authors have no competing interests to declare.

Details

Language :
English
ISSN :
1932-6203
Volume :
15
Issue :
4
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
32275672
Full Text :
https://doi.org/10.1371/journal.pone.0230392