He Ying, Cai Lianying, Liu Liu, Zhang Yuxu, Si Lu, Cheng Qiuchen, Luo Shuangyan
Department of Gastroenterology, The People's Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Zhongshan Street, Qingxiu District, Nanning, 530021, People's Republic of China.
Department of General Practice Medicine, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Immunol Res. 2025 Jun 27;73(1):100. doi: 10.1007/s12026-025-09656-z.
Endoplasmic reticulum (ER) stress induced by hepatitis B virus (HBV) infection is associated with the development of liver fibrosis. Golgi protein 73 (GP73) is increased during HBV infection. Nevertheless, whether GP73 during HBV infection mediates ER stress in liver fibrosis is still poorly understood. TGF-β1 was used to induce HepG2.2.15 cells to establish liver fibrosis cells model. GP73 expression was evaluated using qRT-PCR analysis and Western blot. HepG2.2.15 cells viability and proliferation were assessed via CCK-8 assay and EdU assay, respectively. The protein levels of α-SMA, fibronectin, collagen I and collagen III for liver fibrosis, GRP78, p-PERK, p-eIF2α, ATF4 and CHOP for ER stress, as well as p-Smad2 and Smad2 were evaluated by Western blot. TGF-β1 incubation obviously elevated GP73 expression, while GP73 knockdown reduced the GP73 levels in HBV-transfected HepG2215 cells. GP73 knockdown reversed the effects of TGF-β1 exposure on HepG2.2.15 cells viability and proliferation. The protein levels of liver fibrosis marker, ERS marker and p-Smad2 were remarkably increased following TGF-β1 stimulation, which were counteracted by GP73 silence or the application of 4-phenylbutyric acid (4-PBA). However, these results were opposite after tunicamycin (TM) treatment. In conclusion, knockdown of GP73 potentially impeded the advancement of liver fibrosis via mediating ERs through Smad2 signal pathway.
乙型肝炎病毒（HBV）感染诱导的内质网（ER）应激与肝纤维化的发生发展相关。高尔基体蛋白73（GP73）在HBV感染期间升高。然而，HBV感染期间的GP73是否介导肝纤维化中的内质网应激仍知之甚少。使用转化生长因子-β1（TGF-β1）诱导HepG2.2.15细胞建立肝纤维化细胞模型。通过qRT-PCR分析和蛋白质免疫印迹法评估GP73表达。分别通过细胞计数试剂盒-8（CCK-8）法和5-乙炔基-2'-脱氧尿苷（EdU）法评估HepG2.2.15细胞的活力和增殖。通过蛋白质免疫印迹法评估肝纤维化相关的α-平滑肌肌动蛋白（α-SMA）、纤连蛋白、I型胶原和III型胶原的蛋白水平，内质网应激相关的葡萄糖调节蛋白78（GRP78）、磷酸化蛋白激酶样内质网激酶（p-PERK）、磷酸化真核翻译起始因子2α（p-eIF2α）、活化转录因子4（ATF4）和C/EBP同源蛋白（CHOP），以及磷酸化Smad2和Smad2的蛋白水平。TGF-β1孵育明显提高了GP73表达，而GP73基因敲低降低了HBV转染的HepG2215细胞中的GP73水平。GP73基因敲低逆转了TGF-β1暴露对HepG2.2.15细胞活力和增殖的影响。TGF-β1刺激后，肝纤维化标志物、内质网应激标志物和磷酸化Smad2的蛋白水平显著升高，而GP73沉默或应用4-苯基丁酸（4-PBA）可抵消这些升高。然而，衣霉素（TM）处理后的结果则相反。总之，敲低GP73可能通过Smad2信号通路介导内质网应激来潜在地阻碍肝纤维化的进展。
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