State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
The First People's Hospital of YueYang, Yueyang, Hunan, China.
Sci Rep. 2017 Sep 11;7(1):11084. doi: 10.1038/s41598-017-11541-1.
Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 μm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line. This induction process was mediated by activation of epithelial growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signaling through an EGFR ligand-dependent mechanism. Amphiregulin (AR) was identified as the major ligand responsible for EGFR-ERK signaling activation and MUC5AC expression. In turn, EGFR-ERK pathway activation was found to contribute to the de novo synthesis of AR. This positive feedback loop might play an important role in a sustained mucus hypersecretion response.
生物质燃料烟雾被认为是导致慢性阻塞性肺疾病的原因之一，这种疾病的特征是粘液细胞化生和粘液分泌增强。我们研究了来自木柴烟雾（WSPM2.5）的直径<2.5μm 的颗粒物（PM2.5）对最显著的分泌性粘蛋白 MUC5AC 的表达的影响。木柴烟雾在暴露 3 个月后能够诱导大鼠呼吸道中 MUC5AC 的表达。WSPM2.5 能够诱导原代人呼吸道上皮细胞和 NCI-H292 细胞系中 MUC5AC 的产生。这个诱导过程是通过表皮生长因子受体（EGFR）-细胞外信号调节激酶（ERK）信号的激活来介导的，而这种激活是通过 EGFR 配体依赖性机制发生的。双向调节蛋白（AR）被确定为负责 EGFR-ERK 信号激活和 MUC5AC 表达的主要配体。反过来，EGFR-ERK 通路的激活被发现有助于 AR 的从头合成。这个正反馈回路可能在持续的粘液高分泌反应中发挥重要作用。
