Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.
Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.
复制标题
DOI：
10.3389/fimmu.2018.01348
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Friedland JS
中科院分区：
文献类型：
--
作者：
Brilha S;Chong DLW;Khawaja AA;Ong CWM;Guppy NJ;Porter JC;Friedland JS
肺结核（TB）是由吸入结核分枝杆菌引起的，其破坏支气管上皮屏障以建立局部感染。基质金属蛋白酶-1在结核病的免疫病理学中起着至关重要的作用，导致I型胶原蛋白的分解和空化，但这种胶原酶也可能参与支气管上皮修复。我们假设细胞外基质（ECM）调节M。结核病驱动的人支气管上皮细胞（HBEC）表达基质金属蛋白酶-1，调节呼吸道上皮细胞迁移和修复。来自用M.结核病诱导支气管上皮细胞中的胶原酶活性，当细胞在I型胶原基质上培养时，胶原酶活性降低约87%。基质金属蛋白酶-1具有局灶性定位，这与细胞迁移一致，并且I型胶原的总体分泌减少了32%。金属蛋白酶的特异性组织抑制剂无相关变化。基质金属蛋白酶-1分泌减少是由于配体与α2β1整合素结合，并依赖于肌动蛋白细胞骨架。在肺活检中，来自肺TB患者的样品，整合素α2β1在支气管上皮上高度表达。与胶原蛋白与对照肺相当的区域相比，胶原蛋白基质破坏的肺区域显示基质金属蛋白酶-1表达增加。I型胶原基质增加呼吸道上皮细胞迁移的伤口愈合试验中，这也是基质金属蛋白酶依赖性的，因为它被阻断的基质金属蛋白酶抑制剂GM 6001。总之，我们报道了一种新的机制，通过这种机制，α2β1介导的ECM信号调节HBEC分泌基质金属蛋白酶-1，调节它们在TB中的迁移和上皮修复。
Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.
登录
查看更多内容
DOI：
10.1083/jcb.121.1.163
发表时间：
1993-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Leavesley DI;Schwartz MA;Rosenfeld M;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
15.9
作者：
Elkington, Paul;Shiomi, Takayuki;Friedland, Jon S.
通讯作者：
Friedland, Jon S.
影响因子：
14.5
作者：
Bourboulia D;Stetler-Stevenson WG
通讯作者：
Stetler-Stevenson WG
DOI：
10.1083/jcb.131.3.791
发表时间：
1995-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Miyamoto S;Teramoto H;Coso OA;Gutkind JS;Burbelo PD;Akiyama SK;Yamada KM
通讯作者：
Yamada KM
影响因子：
6.4
作者：
Bao, Wenjie;Stromblad, Staffan
通讯作者：
Stromblad, Staffan