Knockdown of OLFM4 protects cardiomyocytes from sepsis by inhibiting apoptosis and inflammatory responses
Main Article Content
Keywords
myocardial injury, NF-κB pathway, OLFM4, sepsis
Abstract
Sepsis is a systemic inflammatory response that can result in cardiac insufficiency or heart failure known as septic myocardial injury. A previous study identified OLFM4 as an important gene in sepsis through bioinformatics analysis. However, there is limited research on the regulatory functions of OLFM4 in sepsis-triggered myocardial injury, and the related molecular mechanisms remain unclear. In this study, the protein expression of OLFM4 was found to be significantly elevated in LPS-stimulated H9C2 cells, and its suppression enhanced cell proliferation and reduced cell apoptosis in LPS-triggered H9C2 cells. The inflammatory factors TNF-α, IL-6, and IL-1β were increased after LPS treatment, and these effects were mitigated after silencing OLFM4. Moreover, it was confirmed that inhibition of OLFM4 attenuated the NF-κB signaling pathway. In conclusion, the knockdown of OLFM4 protected cardiomyocytes from sepsis by inhibiting apoptosis and inflammatory responses via the NF-κB pathway. These findings provide important insights into the regulatory functions of OLFM4 in the progression of septic myocardial injury.
References
2. Sazonov, V, et al. Case Series: Efficacy and safety of hemoadsorption with ha-330 adsorber in septic pediatric patients with cancer. Front Pediatr. 2021;9:672260. 10.3389/fped.2021.672260
3. Zuccari, S, et al. Changes in cytokines, haemodynamics and microcirculation in patients with sepsis/septic shock undergoing continuous renal replacement therapy and blood purification with cytosorb. Blood Purif. 2020;49(1-2):107-13. 10.1159/000502540
4. Mirijello, A, Tosoni, A, On Behalf Of The Internal Medicine Sepsis Study Group. New strategies for treatment of-sepsis. Medicina. 2020;56(10):527. 10.3390/medicina56100527
5. Carbone, F, et al. Septic cardiomyopathy: from pathophysiology to the clinical setting. Cells. 2022;11(18). 10.3390/cells11182833
6. Hochstadt, A, Meroz Y, Landesberg G. Myocardial dysfunction in severe sepsis and septic shock: more questions than answers? J Cardiothorac Vasc Anesth, 2011;25(3): 526-35. 10.1053/j.jvca.2010.11.026
7. Liu, W, Rodgers, GP. Olfactomedin 4 Is a biomarker for the severity of infectious diseases. Open Forum Infect Dis. 2022;9(4):ofac061. 10.1093/ofid/ofac061
8. Chen, S, et al. Olfactomedin 4 deletion exacerbates nonalcoholic fatty liver disease through P62-dependent mitophagy in mice. Metabolism. 2023;148:155679. 10.1016/j.metabol.2023.155679
9. Ma, HW, et al. Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer. Cancer Gene Ther. 2023;30(5):694-703. 10.1038/s41417-022-00585-9
10. Ren, X, et al. Quantitative proteomic analysis of synovial tissue reveals that upregulated OLFM4 aggravates inflammation in rheumatoid arthritis. J Proteome Res. 2021;20(10):4746-57. 10.1021/acs.jproteome.1c00399
11. Zhang, F, et al. Qinbaohong Zhike oral liquid attenuates LPS-induced acute lung injury in immature rats by inhibiting OLFM4. Oxid Med Cell Longev. 2022;2022:7272371. 10.1155/2022/7272371
12. Gong, F, et al. OLFM4 regulates lung epithelial cell function in sepsis-associated ARDS/ALI via LDHA-mediated NF-κB signaling. J Inflamm Res. 2021;14:7035-51. 10.2147/JIR.S335915
13. Abdelnaser, M, et al. Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury. Naunyn Schmiedebergs Arch Pharmacol, 2024;397(2):947-58. 10.1007/s00210-023-02650-y
14. Fang, X. et al., The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol, 2023;20(1):7-23. 10.1038/s41569-022-00735-4
15. Yu, Y. et al., Hsp22 ameliorates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidative stress, and apoptosis. Bioengineered. 2021;12(2):12544-54. 10.1080/21655979.2021.2010315
16. Qiu, J, et al. Ulinastatin protects against sepsis-induced myocardial injury by inhibiting NLRP3 inflammasome activation. Mol Med Rep. 2021;24(4). 10.1002/iid3.1039
17. Sidheeque Hassan, V, et al. Exogenous fetuin-A protects against sepsis-induced myocardial injury by inhibiting oxidative stress and inflammation in mice. Fundam Clin Pharmacol. 2023;37(3):607-17. 10.1111/fcp.12870
18. Xia, H, et al. MiR-195-5p represses inflammation, apoptosis, oxidative stress, and endoplasmic reticulum stress in sepsis--induced myocardial injury by targeting activating transcription factor 6. Cell Biol Int. 2022;46(2):243-54. 10.1002/cbin.11726
19. Fu, W, et al. Neogambogic acid relieves myocardial injury induced by sepsis via p38 MAPK/NF-κB pathway. Korean J Physiol Pharmacol. 2022;26(6):511-18. 10.4196/kjpp.2022.26.6.511
20. Zhang, SM, et al. Effect of rosiglitazone on myocardial injury in septic rats through NF-κB pathway. Eur Rev Med Pharmacol Sci. 2020;24(1):452-60. 10.26355/eurrev_202001_19945
21. Zhang, C, et al. Inhibition of XBP1 Alleviates LPS-Induced Cardiomyocytes Injury by Upregulating XIAP through Suppressing the NF-κB Signaling Pathway. Inflammation, 2021;44(3):974-84. 10.1007/s10753-020-01392
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.