State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, 430062, China.
Adv Healthc Mater. 2024 May;13(13):e2303957. doi: 10.1002/adhm.202303957. Epub 2024 Feb 19.
Interleukin-37 (IL-37) is a potent anti-inflammatory cytokine belonging to the IL-1 family. This study investigates the regulatory mechanism and reparative effects of IL-37 on HF-related human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) and engineered human heart tissue subjected to hypoxia and HO treatment. The contractile force and Ca conduction capacity of the tissue are assessed using a stretching platform and high-resolution fluorescence imaging system. This investigation reveals that IL-37 treatment significantly enhances cell viability, calcium transient levels, contractile force, and Ca conduction capacity in HF-related hiPSC-CMs and engineered human heart tissue. Notably, IL-37 facilitates the upregulation of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) through enhancing nuclear p-STAT3 levels. This effect is mediated by the binding of p-STAT3 to the SERCA2a promoter, providing a novel insight on the reparative potential of IL-37 in HF. IL-37 demonstrates its ability to enhance systolic function by modulating myocardial calcium handling via the p-STAT3/SERCA2a axis in HF-related engineered human heart tissue (as shown in schematic diagram).
白细胞介素-37 (IL-37) 是一种强大的抗炎细胞因子，属于白细胞介素-1 家族。本研究探讨了 IL-37 对 HF 相关的人诱导多能干细胞衍生心肌细胞 (hiPSC-CMs) 和缺氧及 HO 处理的工程化人心组织的调节机制和修复作用。使用拉伸平台和高分辨率荧光成像系统评估组织的收缩力和 Ca 传导能力。这项研究表明，IL-37 治疗可显著提高 HF 相关 hiPSC-CMs 和工程化人心组织中的细胞活力、钙瞬变水平、收缩力和 Ca 传导能力。值得注意的是，IL-37 通过增强核 p-STAT3 水平促进肌浆网钙 ATP 酶 2a (SERCA2a) 的上调。这种作用是通过 p-STAT3 与 SERCA2a 启动子的结合介导的，为 IL-37 在 HF 中的修复潜力提供了新的见解。IL-37 通过调节 p-STAT3/SERCA2a 轴在 HF 相关的工程化人心组织中增强心肌钙处理，从而显示其增强收缩功能的能力（如图所示）。
