Children's Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325027, Wenzhou, China.
Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Ital J Pediatr. 2023 Jan 4;49(1):2. doi: 10.1186/s13052-022-01401-8.
Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted.
Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation.
In this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model.
Our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD.
川崎病（KD）是一种病因不明的血管炎。鉴于目前 KD 的诊断和治疗策略主要依赖于临床经验，有必要进一步研究其病理机制。
采用酶联免疫吸附试验（ELISA）检测 SIGIRR、TLR4 和 caspase-8 的血清水平。采用 Western blot 法测定蛋白水平，采用流式细胞术分析细胞凋亡。采用苏木精-伊红（HE）染色和 TUNEL 染色分别观察冠状动脉炎症和 DNA 片段化。
本研究发现，KD 患者血清和 KD 血清处理的内皮细胞中 SIGIRR 水平下调。然而，与健康对照（HC）相比，KD 患者血清中的 caspase-8 水平升高。因此，我们假设 SIGIRR-caspase-8 信号通路可能在 KD 病理生理学中发挥重要作用。体外实验表明，KD 条件下内皮细胞凋亡与 caspase-8 激活有关，SIGIRR 过表达通过抑制 caspase-8 激活减轻内皮细胞凋亡。这些发现也在白念珠菌细胞壁提取物（CAWS）诱导的 KD 小鼠模型中得到了验证。
我们的数据表明，SIGIRR-caspase-8 信号介导的内皮细胞凋亡在冠状动脉内皮损伤中起关键作用，为治疗 KD 提供了潜在的靶点。
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