High-mobility group box-1 peptide ameliorates bronchopulmonary dysplasia by suppressing inflammation and fibrosis in a mouse model

Takeya Hara; Takashi Shimbo; Tatsuo Masuda; Tomomi Kitayama; Makoto Fujii; Morifumi Hanawa; Kazuha Yokota; Masayuki Endo; Takuji Tomimatsu; Tadashi Kimura; Katsuto Tamai

doi:10.1016/j.bbrc.2023.06.032

High-mobility group box-1 peptide ameliorates bronchopulmonary dysplasia by suppressing inflammation and fibrosis in a mouse model

Biochem Biophys Res Commun. 2023 Sep 3:671:357-365. doi: 10.1016/j.bbrc.2023.06.032. Epub 2023 Jun 9.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
² Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan.
³ StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan.
⁴ Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, Japan.
⁵ StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; Department of Children's and Women's Health, Division of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
⁶ StemRIM Inc., Ibaraki, Osaka, Japan.
⁷ Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; Department of Children's and Women's Health, Division of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. Electronic address: endo@gyne.med.osaka-u.ac.jp.
⁸ Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. Electronic address: tamai@gts.med.osaka-u.ac.jp.

PMID: 37329659
DOI: 10.1016/j.bbrc.2023.06.032

Abstract

Background: This study aimed to examine the effect of the HMGB1 peptide on Bronchopulmonary dysplasia (BPD)-related lung injury in a mouse model.

Results: HMGB1 peptide ameliorates lung injury by suppressing the release of inflammatory cytokines and decreasing soluble collagen levels in the lungs. Single-cell RNA sequencing showed that the peptide suppressed the hyperoxia-induced inflammatory signature in macrophages and the fibrotic signature in fibroblasts. These changes in the transcriptome were confirmed using protein assays.

Conclusion: Systemic administration of HMGB1 peptide exerts anti-inflammatory and anti-fibrotic effects in a mouse model of BPD. This study provides a foundation for the development of new and effective therapies for BPD.

Keywords: Bronchopulmonary dysplasia; Chronic lung disorder; HMGB1; Mesenchymal stem cell; Peptide; Single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Bronchopulmonary Dysplasia* / drug therapy
Bronchopulmonary Dysplasia* / genetics
Cytokines / adverse effects
Disease Models, Animal
Fibrosis
HMGB1 Protein* / metabolism
Humans
Hyperoxia* / pathology
Infant, Newborn
Inflammation / drug therapy
Inflammation / pathology
Lung / pathology
Lung Injury* / pathology
Mice

Substances

HMGB1 Protein
Cytokines