Regulation of high mobility group box 1 and hypoxia in the migration of mesenchymal stem cells

Abstract Bronchopulmonary dysplasia (BPD) is a chronic lung disorder that affect approximately 40% of preterm infants, with no established curative therapy. The administration of mesenchymal stem cells (MSCs) to BPD patients has shown promising outcomes. Previously, we demonstrated that a synthesized peptide originating from high mobility group box-1 protein (HMGB1) induces a regenerative cascade through activating endogenous MSCs. Here, we tested whether the HMGB1 peptide can ameliorate BPD-related lung injury. In a mouse BPD model established via hyperoxia exposure, three shots of HMGB1 peptide significantly improved survival and suppressed inflammation and fibrosis in the lung. Single-cell RNA-sequencing of the lung further showed that the peptide significantly suppressed a hyperoxia-induced inflammatory signature in macrophages and fibrotic signature in fibroblasts. These changes in the transcriptome were also confirmed at the protein level. Taken together, our data show that treatment with the HMGB1 peptide suppressed inflammation and fibrosis, thus preventing BPD progression. This study serves as a foundation for the development of new effective therapies for BPD.

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The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster

10.1101/390864 ◽

2018 ◽

Author(s):

Takashi Kido ◽

Shigeru Miyagawa ◽

Takasumi Goto ◽

Katsuto Tamai ◽

Takayoshi Ueno ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Dilated Cardiomyopathy ◽

High Mobility ◽

Left Ventricular ◽

High Mobility Group ◽

Hamster Model ◽

Marrow Mesenchymal Stem Cells

AbstractObjectivesWe hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.MethodsTwenty-week-old J2N-k hamsters, which are δ-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).ResultsThe HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor α stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.ConclusionsSystemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.

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The High Mobility Group Protein HMGA2: A Co-Regulator of Chromatin Structure and Pluripotency in Stem Cells?

Stem Cell Reviews and Reports ◽

10.1007/s12015-009-9078-9 ◽

2009 ◽

Vol 5 (3) ◽

pp. 224-230 ◽

Cited By ~ 72

Author(s):

Kurt Pfannkuche ◽

Heike Summer ◽

Ou Li ◽

Jürgen Hescheler ◽

Peter Dröge

Keyword(s):

Stem Cells ◽

Chromatin Structure ◽

High Mobility ◽

High Mobility Group ◽

High Mobility Group Protein ◽

Group Protein

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Epigenetic Contribution of High-Mobility Group A Proteins to Stem Cell Properties

International Journal of Cell Biology ◽

10.1155/2018/3698078 ◽

2018 ◽

Vol 2018 ◽

pp. 1-20 ◽

Cited By ~ 5

Author(s):

Vincenzo Giancotti ◽

Natascha Bergamin ◽

Palmina Cataldi ◽

Claudio Rizzi

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

High Mobility ◽

High Mobility Group ◽

Dna Modification ◽

Epigenetic Factors ◽

Group A ◽

Induced Pluripotent

High-mobility group A (HMGA) proteins have been examined to understand their participation as structural epigenetic chromatin factors that confer stem-like properties to embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and cancer stem cells (CSCs). The function of HMGA was evaluated in conjunction with that of other epigenetic factors such as histones and microRNAs (miRs), taking into consideration the posttranscriptional modifications (PTMs) of histones (acetylation and methylation) and DNA methylation. HMGA proteins were coordinated or associated with histone and DNA modification and the expression of the factors related to pluripotency. CSCs showed remarkable differences compared with ESCs and iPSCs.

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