Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
Respir Res. 2011 Oct 31;12(1):144. doi: 10.1186/1465-9921-12-144.
MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we generated cell lines expressing wild-type or catalytically-inactive mutant MMP28 in two pulmonary epithelial cell lines, A549 and BEAS-2B. We observed that over-expression of MMP28 provided protection against apoptosis induced by either serum-deprivation or treatment with a protein kinase inhibitor, staurosporine. Furthermore, we observed increased caspase-3/7 activity in influenza-infected lungs from Mmp28-/- mice compared to wild-type mice, and this activity localized to the airway epithelium but was not associated with a change in viral load. Thus, we have identified a novel role of MMP28 in promoting epithelial cell survival in the lung.
MMP28 在许多组织中由上皮细胞组成性表达，包括肺的呼吸上皮细胞和皮肤的角质形成细胞。这种组成性表达表明 MMP28 可能在维持上皮细胞稳态中发挥作用。为了确定其在肺上皮细胞生物学中的功能，我们在两种肺上皮细胞系 A549 和 BEAS-2B 中生成了表达野生型或催化失活突变型 MMP28 的细胞系。我们观察到 MMP28 的过表达可提供对血清剥夺或蛋白激酶抑制剂 staurosporine 诱导的细胞凋亡的保护。此外，我们观察到与野生型小鼠相比，Mmp28-/- 小鼠感染流感后的肺中 caspase-3/7 活性增加，并且这种活性定位于气道上皮细胞，但与病毒载量的变化无关。因此，我们已经确定了 MMP28 在促进肺上皮细胞存活中的新作用。
