Zhao Han, Zhang Jiayu, Li Dengliang, Cui Zhanding, Liu Jiuyuan, Bao Di, Wei Yiming, Zhang Xinyue, Wu Zhimin, Zhang Tianqi, Wang Kai, Yi Shushuai, Lian Wei, Hu Guixue
College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
Changchun Chengkai Agricultural Investment Livestock Development Co.,Ltd.,Changchun, China.
PLoS One. 2025 Jan 3;20(1):e0316074. doi: 10.1371/journal.pone.0316074. eCollection 2025.
Porcine epidemic diarrhea virus (PEDV) is a significant pathogen affecting swine, causing severe economic losses worldwide. This study explores the regulatory role of miRNA-328-3p to ZO-1 expression and its impact on PEDV proliferation via the PLC-β1-PKC pathway in IPEC-J2 cells. We found that miRNA-328-3p can target ZO-1, influencing its expression and subsequently affecting the integrity of tight junctions in the cells. Overexpression of PLC-β1, combined with miRNA-328-3p silencing, enhanced ZO-1 expression, while PLC-β1 knockdown combined with miRNA-328-3p overexpression inhibited ZO-1 expression. Furthermore, PLC-β1 overexpression increased both viral genome expression and PEDV titers, whereas its silencing had the opposite effect. Notably, our data indicated a negative correlation between PLC-β1 and PKC expression, and PKC silencing attenuated the upregulatory effect of PLC-β1 on ZO-1. These findings suggest that PLC-β1 modulates ZO-1 expression through the PKC pathway, providing new insights into the molecular mechanisms of PEDV infection and potential therapeutic targets.
猪流行性腹泻病毒（PEDV）是一种影响猪的重要病原体，在全球范围内造成严重经济损失。本研究探讨了miRNA-328-3p对紧密连接蛋白1（ZO-1）表达的调控作用及其通过磷脂酶C-β1（PLC-β1）-蛋白激酶C（PKC）途径对IPEC-J2细胞中PEDV增殖的影响。我们发现miRNA-328-3p可以靶向ZO-1，影响其表达，进而影响细胞紧密连接的完整性。过表达PLC-β1并沉默miRNA-328-3p可增强ZO-1表达，而敲低PLC-β1并过表达miRNA-328-3p则抑制ZO-1表达。此外，过表达PLC-β1可增加病毒基因组表达和PEDV滴度，而沉默PLC-β1则产生相反的效果。值得注意的是，我们的数据表明PLC-β1与PKC表达呈负相关，并且沉默PKC可减弱PLC-β1对ZO-1的上调作用。这些发现表明，PLC-β1通过PKC途径调节ZO-1表达，为PEDV感染的分子机制及潜在治疗靶点提供了新的见解。
