These findings indicate that lung fibroblasts and endothelial cells protect epithelial barrier integrity; however they can not reverse the defect in TEER development by PKD overexpression. Additionally, it appears that IPF and KM 11060 normal lung fibroblasts have a comparable ability to protect epithelial barrier function. IPF, the most common form of the idiopathic interstitial pneumonias, is a chronic, relentlessly progressive and usually fatal lung disease of unknown etiology, and for which no effective treatments exist so far. Although the pathogenic mechanisms that underlie IPF are not clear, a growing body of evidence indicates that IPF is driven by abnormally activated AECs. It is believed that repetitive epithelial injury leads to SAR 7334 aberrant activation of AECs. These AECs produce mediators to stimulate the proliferation of resident mesenchymal cells, to attract circulating fibrocytes, and to promote the epithelial to mesenchymal transition, resulting in the formation of fibroblast and myofibroblast foci. Activated myofibroblasts then secrete excessive amounts of extracellular matrix with the subsequent destruction of the normal lung architecture and the loss of alveolar spaces. It has been shown that the activated AECs, such as hyperplastic type II pneumocytes and regenerative AECs, produce a number of chemokines, cytokines and growth factors, including TGFb, PDGF, TNFa, and endothelin I. In this study, we found that PKD family kinases were increased and activated in the hyperplastic and regenerative AECs lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts compared with regenerative AECs. These findings indicate that expression levels of PKD family kinases differs in mesenchymal cells within the injured lung and suggest that the proportion of epithelial cells that have undergone mesenchymal transition likely lose expression of these kinases as part of the phenotypic change. While the differences between epithelial and mesenchymal cell expression of PKD family kinases were clear, the findings in isolated cells were not tested, representing a potential limitation of these analyses. It is possible, however, that the isolation procedures could affect expression of these kinases, so we relied on immunohistichemical analyses as our primary assessment.