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DOI :10.26650/experimed.1427537   IUP :10.26650/experimed.1427537    Tam Metin (PDF)

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

Zeliha Emrence, Şeyma Punar, Eylem Taşkın, Celal Güven, Melda Sarıman, Neslihan Abacı

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.

Anahtar Kelimeler: Adriamycin, cardiotoxicity, CXCL12, CXCR4, CXCR7, gene expression, HMGB1

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Referanslar

  • 1. Shi Y, Riese DJ, Shen J. The role of the CXCL12/CXCR4/CXCR7 chemokine axis in cancer. Front Pharmacol 2020; 11: 574667. google scholar
  • 2. Huynh C, Dingemanse J, Meyer zu Schwabedissen HE, Sidharta PN. Relevance of the CXCR4/CXCR7-CXCL12 axis and its effect in pathophysiological conditions. Pharmacol Res 2020; 161: 105092. google scholar
  • 3. Segret A, Rücker-Martin C, Pavoine C, Flavigny J, Deroubaix E, Châtel MA, et al. Structural localization and expression of CXCL12 and CXCR4 in rat heart and isolated cardiac myocytes. J Histochem Cytochem 2007; 55(2): 141-50. google scholar
  • 4. De Leo F, Quilici G, Tirone M, De Marchis F, Mannella V, Zucchelli C, et al. Diflunisal targets the HMGB 1/ CXCL 12 heterocomplex and blocks immune cell recruitment. EMBO Rep 2019; 20(10): 47788. google scholar
  • 5. Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P, Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev 2017; 280(1): 74-82. google scholar
  • 6. Gardella S, Andrei C, Ferrera D, Lotti L V, Torrisi MR, Bianchi ME, et al. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 2002; 3(10): 995-1001. google scholar
  • 7. Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 2012; 209(3): 551-63. google scholar
  • 8. Mordente A, Meucci E, Martorana GE, Giardina B, Minotti G. Human heart cytosolic reductases and anthracycline cardiotoxicity. IUBMB Life 2001; 52(1-2): 83-8. google scholar
  • 9. Gao Y, Shang Q, Li W, Guo W, Stojadinovic A, Mannion C, et al. Antibiotics for cancer treatment: A double-edged sword. J Cancer 2020; 11(17): 5135-49. google scholar
  • 10. Luo P, Zhu Y, Chen M, Yan H, Yang B, Yang X, et al. HMGB1 contributes to adriamycin-induced cardiotoxicity via up-regulating autophagy. Toxicol Lett 2018; 292:115-22. google scholar
  • 11. Mitry MA, Edwards JG. Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int J Cardiol Heart Vasc 2016; 10: 17-24 google scholar
  • 12. Taskin E, Guven C, Kaya ST, Sariman M, Emrence Z, Sirma Ekmekci S, et al. Silencing HMGB1 expression inhibits adriamycin’s heart toxicity via TLR4 dependent manner through MAPK signal transduction. JBUON 2020; 25(1): 554-65. google scholar
  • 13. Qin WD, Mi SH, Li C, Wang GX, Zhang JN, Wang H, et al. Low shear stress induced HMGB1 translocation and release via PECAM-1/ PARP-1 pathway to induce inflammation response. PLoS One 2015; 10(3): 0120586 google scholar
  • 14. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25(4): 402-8. google scholar
  • 15. Bhagat A, Shrestha P, Kleinerman ES. The innate immune system in cardiovascular diseases and its role in doxorubicin-induced cardiotoxicity. Int J Mol Sci 2022; 23(23): 14649. google scholar
  • 16. Rosales C. Neutrophil: A cell with many roles in inflammation or several cell types? Front Physiol 2018; 9: 113. google scholar
  • 17. Beji S, Milano G, Scopece A, Cicchillitti L, Cencioni C, Picozza M, et al. Doxorubicin upregulates CXCR4 via miR-200c/ZEB1-dependent mechanism in human cardiac mesenchymal progenitor cells. Cell Death Dis 2017; 8(8): 3020. google scholar
  • 18. Mezzapelle R, Leo M, Caprioglio F, Colley LS, Lamarca A, Sabatino L, et al. CXCR4/CXCL12 activities in the tumor microenvironment and implications for tumor immunotherapy. Cancers (Basel) 2022; 14(9): 2314. google scholar

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DIŞA AKTAR



APA

Emrence, Z., Punar, Ş., Taşkın, E., Güven, C., Sarıman, M., & Abacı, N. (2024). Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity. Experimed, 14(2), 63-67. https://doi.org/10.26650/experimed.1427537


AMA

Emrence Z, Punar Ş, Taşkın E, Güven C, Sarıman M, Abacı N. Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity. Experimed. 2024;14(2):63-67. https://doi.org/10.26650/experimed.1427537


ABNT

Emrence, Z.; Punar, Ş.; Taşkın, E.; Güven, C.; Sarıman, M.; Abacı, N. Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity. Experimed, [Publisher Location], v. 14, n. 2, p. 63-67, 2024.


Chicago: Author-Date Style

Emrence, Zeliha, and Şeyma Punar and Eylem Taşkın and Celal Güven and Melda Sarıman and Neslihan Abacı. 2024. “Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity.” Experimed 14, no. 2: 63-67. https://doi.org/10.26650/experimed.1427537


Chicago: Humanities Style

Emrence, Zeliha, and Şeyma Punar and Eylem Taşkın and Celal Güven and Melda Sarıman and Neslihan Abacı. “Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity.” Experimed 14, no. 2 (Nov. 2024): 63-67. https://doi.org/10.26650/experimed.1427537


Harvard: Australian Style

Emrence, Z & Punar, Ş & Taşkın, E & Güven, C & Sarıman, M & Abacı, N 2024, 'Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity', Experimed, vol. 14, no. 2, pp. 63-67, viewed 15 Nov. 2024, https://doi.org/10.26650/experimed.1427537


Harvard: Author-Date Style

Emrence, Z. and Punar, Ş. and Taşkın, E. and Güven, C. and Sarıman, M. and Abacı, N. (2024) ‘Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity’, Experimed, 14(2), pp. 63-67. https://doi.org/10.26650/experimed.1427537 (15 Nov. 2024).


MLA

Emrence, Zeliha, and Şeyma Punar and Eylem Taşkın and Celal Güven and Melda Sarıman and Neslihan Abacı. “Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity.” Experimed, vol. 14, no. 2, 2024, pp. 63-67. [Database Container], https://doi.org/10.26650/experimed.1427537


Vancouver

Emrence Z, Punar Ş, Taşkın E, Güven C, Sarıman M, Abacı N. Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity. Experimed [Internet]. 15 Nov. 2024 [cited 15 Nov. 2024];14(2):63-67. Available from: https://doi.org/10.26650/experimed.1427537 doi: 10.26650/experimed.1427537


ISNAD

Emrence, Zeliha - Punar, Şeyma - Taşkın, Eylem - Güven, Celal - Sarıman, Melda - Abacı, Neslihan. “Exploring the Relationship Between HMGB1, CXCL12, CXCR4, and CXCR7 in the Context of Adriamycin-Induced Cardiotoxicity”. Experimed 14/2 (Nov. 2024): 63-67. https://doi.org/10.26650/experimed.1427537



ZAMAN ÇİZELGESİ


Gönderim30.01.2024
Kabul28.03.2024
Çevrimiçi Yayınlanma28.05.2024

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