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

Kido, T.; Miyagawa, S.; Goto, T.; Tamai, K.; Ueno, T.; Toda, K.; Kuratani, T.; Sawa, Y.

doi:10.1101/390864

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bioRxiv · 10.1101/390864

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

Kido, T.·Miyagawa, S.·Goto, T.·Tamai, K.·Ueno, T.·Toda, K.·Kuratani, T.·Sawa, Y.

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Abstract

ObjectivesWe 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.\n\nMethodsTwenty-week-old J2N-k hamsters, which are {delta}-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).\n\nResultsThe 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 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.\n\nConclusionsSystemic 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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Kido, T., Miyagawa, S., Goto, T., Tamai, K., Ueno, T., Toda, K., Kuratani, T., Sawa, Y.. 2018-08-13. 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. https://doi.org/10.1101/390864

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