Toll样受体-MYD88信号通路、干细胞基因和klotho的上调介导脓毒症相关的心肌炎症。
Upregulation of TLR-MYD88 signaling, stem cell genes, and Klotho mediates sepsis-associated myocardial inflammation.
作者信息
Mylonas Konstantinos S, Peroulis Michail, Schizas Dimitrios, Boletis John N, Kapelouzou Alkistis
机构信息
Department of Cardiac Surgery, Onassis Cardiac Surgery Center, Athens, Greece.
First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
出版信息
Mol Biol Rep. 2025 Jun 12;52(1):586. doi: 10.1007/s11033-025-10699-6.
BACKGROUND
Sepsis-induced myocardial inflammation involves complex molecular mechanisms that remain incompletely understood.
METHODS
This study examined the dynamic temporal expression of critical inflammatory markers, including Toll-like receptors (TLRs), MYD88, Klotho, and stem cell-associated genes (KLF4, HOXA5, NANOG, and HIF1α) within a cecal ligation and puncture-induced murine model of sepsis.
RESULTS
TLR2, TLR3, TLR4, TLR7 and MYD88 exhibited progressive upregulation across 24, 48, and 72 h, highlighting their pivotal role in inflammatory signaling. Klotho expression increased significantly during sepsis, stabilizing at later stages, suggesting a potential modulatory role. Stem cell-associated genes showed dynamic patterns, with KLF4 and NANOG displaying sustained elevation, HOXA5 peaking at 48 h, and HIF1α progressively rising to its highest levels at 72 h.
CONCLUSIONS
These findings underscore the interplay between inflammatory pathways and metabolic adaptation in sepsis-induced myocardial injury, potentially providing a foundation for targeted therapeutic strategies.
背景
脓毒症诱导的心肌炎症涉及复杂的分子机制，目前仍未完全了解。
方法
本研究在盲肠结扎和穿刺诱导的小鼠脓毒症模型中，检测了关键炎症标志物的动态时间表达，包括Toll样受体（TLRs）、髓样分化因子88（MYD88）、klotho蛋白以及干细胞相关基因（KLF4、HOXA5、NANOG和低氧诱导因子1α（HIF1α））。
结果
TLR2、TLR3、TLR4、TLR7和MYD88在24、48和72小时内呈现进行性上调，突出了它们在炎症信号传导中的关键作用。Klotho蛋白表达在脓毒症期间显著增加，并在后期趋于稳定，提示其具有潜在的调节作用。干细胞相关基因呈现动态变化模式，KLF4和NANOG持续升高，HOXA5在48小时达到峰值，HIF1α在72小时逐渐升至最高水平。
结论
这些发现强调了脓毒症诱导的心肌损伤中炎症途径与代谢适应之间的相互作用，可能为靶向治疗策略提供基础。
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