Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice.
Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice.
复制标题
DOI：
10.3109/08958378.2011.584919
复制
发表时间：
2011-07
影响因子：
2.1
通讯作者：
Liu RM
中科院分区：
文献类型：
--
作者：
Katre A;Ballinger C;Akhter H;Fanucchi M;Kim DK;Postlethwait E;Liu RM
臭氧（O3）是一种常见的环境污染物，已被证明可在不同的动物模型中诱导肺纤维化;然而，其潜在机制仍不清楚。为了研究O3诱导肺纤维化的分子机制，将6至8周龄的C57 BL/6雄性小鼠暴露于由2天过滤空气和5天O3暴露组成的循环O3暴露方案（0.5 ppm，8 h/天）持续5和10个周期，伴或不伴IN-1233腹膜内注射，一种转化生长因子β（TGF-β）1型受体的特异性抑制剂，TGF-β是最有效的促纤维化细胞因子。结果显示，5或10个周期的O3暴露增加了上皮衬里液（ELF）中TGF-β蛋白水平，与纤溶酶原激活物抑制剂1（PAI-1）的表达增加有关，PAI-1是一种TGF-β反应基因，在各种病理条件下的纤维化发展中起关键作用。循环O3暴露也增加了气道壁中胶原和α-平滑肌肌动蛋白（α-SMA）的沉积。然而，这些纤维化的变化并不明显，直到10个周期的O3暴露。重要的是，用IN-1233阻断TGF-β信号通路可抑制O3诱导的Smad 2/3磷酸化、派-1表达以及肺中胶原和α-SMA沉积。我们的数据首次表明，O3暴露增加TGF-β表达并激活TGF-β信号通路，从而介导体内O3诱导的肺纤维化反应。
Ozone (O3), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O3-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O3 exposure protocol consisting of 2 days of filtered air and 5 days of O3 exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O3 exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O3 exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O3 exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O3-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O3 exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O3-induced lung fibrotic responses in vivo.
登录
查看更多内容
影响因子：
3.8
作者：
Fanucchi, MV;Buckpitt, AR;Plopper, CG
通讯作者：
Plopper, CG
影响因子：
6
作者：
Chuang-Tsai, S;Sisson, TH;Simon, RH
通讯作者：
Simon, RH
影响因子：
15.9
作者：
Eitzman, DT;McCoy, RD;Simon, RH
通讯作者：
Simon, RH
DOI：
10.1165/ajrcmb.27.2.4674
发表时间：
2002-08-01
影响因子：
6.4
作者：
Kolb, M;Bonniaud, P;Gauldie, J
通讯作者：
Gauldie, J
影响因子：
24.3
作者：
Bergeron, A;Soler, P;Tazi, A
通讯作者：
Tazi, A