Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity

Abstract

Objective: High-mobility group box-1 (HMGB1), known as an abundant and highly conserved nuclear protein, plays a pivotal role in initiating inflammation, tissue healing, and the immune response following various forms of cell damage. The chemokine C-X-C motif chemokine ligand 12 (CXCL12) forms a signaling axis known as CXCL12/ CXCR4/CXCR7, along with the receptors CXCR4 and CXCR7. Our study aimed to explore the connection between HMGB1 and the involved chemokine axis, CXCR4, CXCL12, and CXCR7, in the context of adriamycin-induced cardiotoxicity. Materials and Methods: We performed RNA interference to suppress HMGB1 expression in H9c2 cardiac myoblast cells. Adriamycin, an anti-tumor antibiotic known for causing cardiotoxicity, was used in conjunction with HMGB1 suppression. We investigated the combined and individual effects of these factors. Gene expression analysis was conducted through qRT-PCR 36 and 48 h post-treatment. Results: Adriamycin treatment increased the expression of CXCL12, CXCR4, and CXCR7. Notably, our study observed significant changes in gene expression when HMGB1 was downregulated and adriamycin was administered. These findings suggest potential molecular mechanisms associated with adriamycin-induced cardiotoxicity, emphasizing the significance of the CXCR4/CXCL12 axis and the impact of HMGB1 modulation. Conclusion: Our study provides insights into the molecular interplay between HMGB1 and the CXCL12/CXCR4/CXCR7 ligand-receptor axis in the context of adriamycin-induced cardiotoxicity. The results shed light on further research to enhance therapeutic approaches or advance new strategies to address this cardiotoxicity.

Keywords

• Adriamycin
• cardiotoxicity
• CXCL12
• CXCR4
• CXCR7
• gene expression
• HMGB1

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