GP73 regulates Hepatic Steatosis by enhancing SCAP-SREBPs interaction.

Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency. Consistent with these functional findings, GP73 blockage could alleviate tunicamycin-induced liver steatosis by reducing SREBPs activation. A significant positive correlation of GP73 with genes in lipid metabolism pathway was also identified in liver cancer based on data from The Cancer Genome Atlas (TCGA) dataset. Our findings revealed previously unrecognized role of GP73 in lipid metabolism.

高尔基体磷蛋白2（GP73，也称为GOLPH2或GOLM1）在血清和肝脏中的表达升高可由病毒感染和细胞因子治疗诱导，与肝脏疾病密切相关，包括急性肝炎、肝硬化和肝细胞癌（HCC）。然而，其在肝脏疾病中的致病作用从未得到详细阐明。在此，我们发现上调的GP73对固醇调节元件结合蛋白（SREBPs）的激活和脂肪生成是必不可少的。值得注意的是，即使在胆固醇充足的情况下，GP73过表达也会增强SREBP裂解激活蛋白（SCAP）-SREBPs的结合及其在高尔基体的运输。与这些功能发现一致，阻断GP73可通过降低SREBPs的激活来缓解衣霉素诱导的肝脏脂肪变性。基于癌症基因组图谱（TCGA）数据集的数据，在肝癌中还发现了GP73与脂质代谢途径中的基因存在显著正相关。我们的研究结果揭示了GP73在脂质代谢中先前未被认识的作用。