| First Author | Buonfiglio LG | Year | 2016 |
| Journal | Am J Respir Cell Mol Biol | Volume | 55 |
| Issue | 6 | Pages | 869-877 |
| PubMed ID | 27486964 | Mgi Jnum | J:253792 |
| Mgi Id | MGI:6101234 | Doi | 10.1165/rcmb.2015-0006OC |
| Citation | Buonfiglio LG, et al. (2016) Protein Kinase Czeta Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury. Am J Respir Cell Mol Biol 55(6):869-877 |
| abstractText | Protein kinase Czeta (PKCzeta) is highly expressed in the lung, where it plays several regulating roles in the pathogenesis of acute lung injury (ALI). Proliferation and differentiation of integrin beta4(+) distal lung epithelial progenitor cells seem to play a key role in proper lung regeneration. We investigated the effects of a myristoylated PKCzeta inhibitor (PKCzetai) in a murine model of bleomycin-induced ALI. After intratracheal injury, we treated mice three times a week with PKCzetai or its vehicle, DMSO. We found that mice injured with bleomycin and then treated with PKCzetai for one week showed decreased activation of PKCzeta, improved lung compliance, and decreased lung protein permeability compared to injured mice treated with DMSO. Mice treated continuously with PKCzetai for 6 weeks showed reduced evidence of lung fibrosis by computed tomographic images, decreased lung collagen deposition, and decreased active transforming growth factor-beta in the bronchoalveolar lavage fluid. In addition, we found an increased number of lung beta4(+) cells compared to DMSO at Week 6. Therefore, we grew isolated integrin beta4(+) lung progenitor cells in the presence of PKCzetai or DMSO and found that beta4(+) cells treated with PKCzetai proliferated more in vitro compared to DMSO. We conclude that the use of a PKCzetai promotes resolution of lung fibrosis in a bleomycin ALI model and increases the number of beta4(+) progenitor cells with regenerative potential in the lung. |
