Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

Veterinary Research

Yong Xiang¹  Qingbo Li¹  Yu Li¹  Zeng Jiang¹  Jinqun Li¹  Canxin Liang¹  Yun Yu¹  Jian Chen¹  Xiaoyan Chen¹  Weisheng Cao² 

[1] College of Veterinary Medicine, South China Agricultural University, 510642, Guangzhou, China;College of Veterinary Medicine, South China Agricultural University, 510642, Guangzhou, China;Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural University, 510642, Guangzhou, China;Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, 510642, Guangzhou, China;National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, South China Agricultural University, 510642, Guangzhou, China;Key Laboratory of Veterinary Vaccine Innovation of the Ministry of Agriculture, 510642, Guangzhou, China;

关键词: chicken telomerase reverse transcriptase;    Wnt/β-catenin signalling pathway;    cell proliferation;    apoptosis;    avian leukosis virus subgroup J;   

DOI  :  10.1186/s13567-021-00979-x

来源: Springer

【 摘 要 】

This study aimed to explore the mutual regulation between chicken telomerase reverse transcriptase (chTERT) and the Wnt/β-catenin signalling pathway and its effects on cell growth and avian leukosis virus subgroup J (ALV-J) replication in LMH cells. First, LMH cells stably overexpressing the chTERT gene (LMH-chTERT cells) and corresponding control cells (LMH-NC cells) were successfully constructed with a lentiviral vector expression system. The results showed that chTERT upregulated the expression of β-catenin, Cyclin D1, TCF4 and c-Myc. chTERT expression level and telomerase activity were increased when cells were treated with LiCl. When the cells were treated with ICG001 or IWP-2, the activity of the Wnt/β-catenin signalling pathway was significantly inhibited, and chTERT expression and telomerase activity were also inhibited. However, when the β-catenin gene was knocked down by small interfering RNA (siRNA), the changes in chTERT expression and telomerase activity were consistent with those in cells treated with ICG001 or IWP-2. These results indicated that chTERT and the Wnt/β-catenin signalling pathway can be mutually regulated. Subsequently, we found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX; upregulating BCL-2 and BCL-X expression; and promoting autophagy. Moreover, chTERT significantly enhanced the migration ability of LMH cells, upregulated the protein and mRNA expression of ALV-J and increased the virus titre. ALV-J replication promoted chTERT expression and telomerase activity.

【 授权许可】

CC BY