He Xue, Li Tiao, Luo Lijuan, Zeng Huihui, Chen Yan, Cai Shan
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Research Unit of Respiratory Disease, Central South University, Changsha, China.
Tob Induc Dis. 2020 Feb 4;18:8. doi: 10.18332/tid/116413. eCollection 2020.
Smoke-driven lung inflammation is considered to be the major pathophysiology mechanism of Chronic Obstructive Pulmonary Disease (COPD)/emphysema. Protein arginine methyltransferase 6 (PRMT6) is a key epigenetic enzyme, which is related to protecting the tri-methylation of H3K4 (H3K4me3). We hypothesized that PTMT6 protects lung inflammation through the nuclear factor kappa B (NF-κB) pathway.
Mice were injected with cigarette smoke extract (CSE) or PBS to establish a mice model, intratracheally instilled with overexpressed PRMT6 or negative control vector. Morphometry of lung slides and lung function were measured. We determined the protein expression of PRMT6 and its related histone targets, the activation of NF-κB pathway, the level of tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β).
After PRMT6 overexpression, the morphometry indexes and lung function were improved. Also, the expression of H3K4me3 was decreased. Overexpressed PRMT6 could suppress CSE-induced NF-κB activation and pro-inflammation genes expression.
The overexpressed PRMT6 could serve as an inflammation inhibitor, potentially through blocking the NF-κB/p65 pathway in the murine emphysema model.
烟雾驱动的肺部炎症被认为是慢性阻塞性肺疾病（COPD）/肺气肿的主要病理生理机制。蛋白质精氨酸甲基转移酶6（PRMT6）是一种关键的表观遗传酶，与保护组蛋白H3第4位赖氨酸三甲基化（H3K4me3）有关。我们假设PRMT6通过核因子κB（NF-κB）途径保护肺部炎症。
给小鼠注射香烟烟雾提取物（CSE）或磷酸盐缓冲液（PBS）以建立小鼠模型，经气管内滴注过表达的PRMT6或阴性对照载体。测量肺组织切片形态学指标和肺功能。我们检测了PRMT6及其相关组蛋白靶点的蛋白表达、NF-κB途径的激活情况、肿瘤坏死因子α（TNFα）和白细胞介素-1β（IL-1β）的水平。
PRMT6过表达后，形态学指标和肺功能得到改善。此外，H3K4me3的表达降低。过表达的PRMT6可抑制CSE诱导的NF-κB激活和促炎基因表达。
过表达的PRMT6可能通过阻断小鼠肺气肿模型中的NF-κB/p65途径，起到炎症抑制剂的作用。
