C1q/TNF-related protein 9 (CTRP9) is implicated in diverse cardiovascular diseases, but its role in viral myocarditis (VMC) is not well explored. This study is aimed at investigating the role and potential mechanism of CTRP9 in VMC. Herein, we found that the peripheral blood collected from children with VMC had lower CTRP9 levels than that from children who had recovered from VMC. H9c2 cardiomyocytes treated with coxsackievirus B3 (CVB3) were applied to establish a VMC model in vitro, and the expression of CTRP9 was significantly decreased in CVB3-induced H9c2 cells. The overexpression of CTRP9 attenuated CVB3-induced apoptosis, inflammation, and fibrosis reactions in H9c2 cells by promoting cell proliferation, reducing the cell apoptosis rate, and inhibiting inflammatory cytokine levels and fibrosis-related gene expression. Moreover, we found that thrombospondin 1 (THBS1) levels were increased in children with VMC, and CTRP9 negatively regulated THBS1 expression by interacting with THBS1. The downregulation of THBS1 inhibited CVB3-induced apoptosis, inflammation, and fibrosis in H9c2 cells. In addition, our mechanistic investigation indicated that the overexpression of THBS1 impaired the inhibitory effect of CTRP9 on CVB3-induced H9c2 cells. The results further revealed that the CVB3-induced NF-κB and TGF-β1/Smad2/3 signaling pathways of H9c2 cells were blocked by CTRP9 yet activated by THBS1. In conclusion, CTRP9 protected H9c2 cells from CVB3-induced injury via the NF-κB and TGF-β1/Smad2/3 signaling pathways by modulating THBS1.

中文翻译：

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C1q/TNF 相关蛋白 9 通过调节 THBS1 通过 NF-κB 和 TGF-β1/Smad2/3 抑制柯萨奇病毒 B3 诱导的心肌细胞损伤


C1q/TNF 相关蛋白 9 (CTRP9) 与多种心血管疾病有关，但其在病毒性心肌炎 (VMC) 中的作用尚未得到充分研究。本研究旨在探讨CTRP9在VMC中的作用和潜在机制。在此，我们发现从 VMC 儿童采集的外周血 CTRP9 水平低于 VMC 康复儿童的外周血 CTRP9 水平。采用柯萨奇病毒B3（CVB3）处理的H9c2心肌细胞建立体外VMC模型，CVB3诱导的H9c2细胞中CTRP9的表达显着降低。 CTRP9的过表达通过促进细胞增殖、降低细胞凋亡率、抑制炎症细胞因子水平和纤维化相关基因表达来减弱CVB3诱导的H9c2细胞的凋亡、炎症和纤维化反应。此外，我们发现 VMC 儿童中血小板反应蛋白 1 (THBS1) 水平升高，并且 CTRP9 通过与 THBS1 相互作用负向调节 THBS1 表达。 THBS1 的下调抑制了 CVB3 诱导的 H9c2 细胞凋亡、炎症和纤维化。此外，我们的机制研究表明，THBS1 的过度表达削弱了 CTRP9 对 CVB3 诱导的 H9c2 细胞的抑制作用。结果进一步表明，CVB3诱导的H9c2细胞的NF- κB和TGF- β1 /Smad2/3信号通路被CTRP9阻断，但被THBS1激活。总之，CTRP9 通过调节 THBS1，通过 NF- κ B 和 TGF- β 1/Smad2/3 信号通路保护 H9c2 细胞免受 CVB3 诱导的损伤。