Liu B, Xiang L, Ji J, et al, Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2, The Journal of clinical investigation, 2021. (IF: 13.4)

Abstract: This article reports that through transcriptomic analysis, it was found that the expression of Sparcl1 in the white adipose tissue (WAT) of NASH mice increases, and the level of Sparcl1 in the plasma of NASH patients is elevated, positively correlating with liver pathological features. Functional experiments show that chronic injection of recombinant Sparcl1 protein or overexpression of Sparcl1 exacerbates liver inflammation and damage in mice, while genetic ablation or knockdown of Sparcl1 and treatment with Sparcl1-neutralizing antibodies can significantly improve the pathogenesis of NASH. The study reveals that Sparcl1 promotes the expression of CCL2 in hepatocytes by binding to TLR4 and activating the NF-κB/p65 signaling pathway, thereby affecting the progression of NASH. Blocking the CCL2/CCR2 pathway can alleviate the hepatic inflammatory response caused by Sparcl1.

摘要：本文通过转录组分析发现，NASH小鼠的白色脂肪组织（WAT）中Sparcl1的表达增加，且NASH患者血浆中Sparcl1水平升高，与肝脏病理特征正相关。功能实验显示，慢性注射重组Sparcl1蛋白或Sparcl1过表达加剧了小鼠的肝脏炎症和损伤，而Sparcl1的遗传消融或敲低以及Sparcl1中和抗体的治疗则可显著改善NASH的发病过程。研究揭示了Sparcl1通过与TLR4结合并激活NF-κB/p65信号通路，促进肝细胞中CCL2的表达，进而影响NASH的进展。阻断CCL2/CCR2途径能够减轻Sparcl1引起的肝脏炎症反应。