Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells.
Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells.
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双调蛋白-EGFR-ERK通路的正反馈介导木烟中的PM2.5诱导上皮细胞中MUC5AC的表达
DOI：
10.1038/s41598-017-11541-1
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发表时间：
2017-09-11
影响因子：
4.6
通讯作者：
Ran P
中科院分区：
文献类型：
--
作者：
Huang L;Pu J;He F;Liao B;Hao B;Hong W;Ye X;Chen J;Zhao J;Liu S;Xu J;Li B;Ran P
生物质燃料烟雾被认为有助于慢性阻塞性肺病，其特征在于粘液细胞化生和粘液分泌增加。我们研究了来自木材烟雾（WSPM 2.5）的直径<2.5 μm（PM2.5）的颗粒物（PM）对最突出的分泌粘蛋白MUC 5AC表达的影响。暴露3个月后，木材烟雾能够诱导大鼠呼吸道中MUC 5AC的表达。WSPM 2.5可以诱导原代人气道上皮细胞和NCI-H292细胞系中的MUC 5AC产生。这一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）信号转导的激活介导的，该信号转导通过EGFR配体依赖性机制进行。双调蛋白（AR）被鉴定为负责EGFR-ERK信号激活和MUC 5AC表达的主要配体。反过来，发现EGFR-ERK通路激活有助于AR的从头合成。这种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。
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.
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DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
DOI：
10.1164/rccm.200603-381oc
发表时间：
2007-01-01
影响因子：
24.7
作者：
de Marco, Roberto;Accordini, Simone;Burney, Peter
通讯作者：
Burney, Peter
影响因子：
10
作者：
Kocbach, Anette;Li, Yanjun;Namork, Ellen
通讯作者：
Namork, Ellen
影响因子：
10
作者：
Guerra S;Sherrill DL;Venker C;Ceccato CM;Halonen M;Martinez FD
通讯作者：
Martinez FD
DOI：
10.1164/rccm.201211-2004oc
发表时间：
2013-04-01
影响因子：
24.7
作者：
Gan, Wen Qi;FitzGerald, J. Mark;Brauer, Michael
通讯作者：
Brauer, Michael