Zeng Ruifeng, Jin Chengli, Zheng Chuchu, Li Shaoqi, Qian Siyue, Pan Jingsa, Wang Lvhe, Zhao Junfeng, Qin Le
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of First Clinical Medical School, Wenzhou Medical University, Wenzhou, China.
Front Cell Dev Biol. 2021 Aug 26;9:683209. doi: 10.3389/fcell.2021.683209. eCollection 2021.
Octamer-binding transcription factor 4 (OCT4) and cancerous inhibitor of protein phosphatase 2A (CIP2A) are upregulated in testicular cancer and cell lines. However, its contribution to orchitis (testicular inflammation) is unclear and was thus, investigated herein. Cell-based experiments on a lipopolysaccharide (LPS)-induced orchitis mouse model revealed robust inflammation, apoptotic cell death, and redox disorder in the Leydig (interstitial), Sertoli (supporting), and, germ cells. Meanwhile, real-time quantitative PCR revealed low OCT4 and CIP2A levels in testicular tissue and LPS-stimulated cells. A gain-of-function study showed that OCT4 overexpression not only increased CIP2A expression but also repressed LPS-induced inflammation, apoptosis, and redox disorder in the aforementioned cells. Furthermore, the re-inhibition of CIP2A expression by TD-19 in OCT4-overexpressing cells counteracted the effects of OCT4 overexpression on inflammation, apoptosis, and redox equilibrium. In addition, our results indicated that the Keap1-Nrf2-HO-1 signaling pathway was mediated by OCT4 and CIP2A. These findings provide insights into the potential mechanism underlying OCT4- and CIP2A-mediated testicular inflammation.
八聚体结合转录因子4（OCT4）和蛋白磷酸酶2A癌性抑制剂（CIP2A）在睾丸癌及细胞系中表达上调。然而，其对睾丸炎（睾丸炎症）的作用尚不清楚，因此本文对此展开研究。在脂多糖（LPS）诱导的睾丸炎小鼠模型上进行的细胞实验显示，睾丸间质细胞、支持细胞和生殖细胞出现了强烈的炎症、凋亡性细胞死亡及氧化还原紊乱。同时，实时定量PCR显示睾丸组织和LPS刺激的细胞中OCT4和CIP2A水平较低。功能获得性研究表明，OCT4过表达不仅增加了CIP2A的表达，还抑制了上述细胞中LPS诱导的炎症、凋亡及氧化还原紊乱。此外，在OCT4过表达细胞中，TD-19对CIP2A表达的再抑制抵消了OCT4过表达对炎症、凋亡及氧化还原平衡的影响。另外，我们的结果表明，Keap1-Nrf2-HO-1信号通路由OCT4和CIP2A介导。这些发现为OCT4和CIP2A介导睾丸炎症的潜在机制提供了见解。
