BackgroundThe airway epithelial cell plays a central role in coordinating the pulmonary response to injury and inflammation. Here, transforming growth factor-β (TGFβ) activates gene expression programs to induce stem cell-like properties, inhibit expression of differentiated epithelial adhesion proteins and express mesenchymal contractile proteins. This process is known as epithelial mesenchymal transition (EMT); although much is known about the role of EMT in cellular metastasis in an oncogene-transformed cell, less is known about Type II EMT, that occurring in normal epithelial cells. In this study, we applied next generation sequencing (RNA-Seq) in primary human airway epithelial cells to understand the gene program controlling Type II EMT and how cytokine-induced inflammation modifies it.ResultsGeneralized linear modeling was performed on a two-factor RNA-Seq experiment of 6 treatments of telomerase immortalized human small airway epithelial cells (3 replicates). Using a stringent cut-off, we identified 3,478 differentially expressed genes (DEGs) in response to EMT. Unbiased transcription factor enrichment analysis identified three clusters of EMT regulators, one including SMADs/TP63 and another NF-κB/RelA. Surprisingly, we also observed 527 of the EMT DEGs were also regulated by the TNF-NF-κB/RelA pathway. This Type II EMT program was compared to Type III EMT in TGFβ stimulated A549 alveolar lung cancer cells, revealing significant functional differences. Moreover, we observe that Type II EMT modifies the outcome of the TNF program, reducing IFN signaling and enhancing integrin signaling. We confirmed experimentally that TGFβ-induced the NF-κB/RelA pathway by observing a 2-fold change in NF-κB/RelA nuclear translocation. A small molecule IKK inhibitor blocked TGFβ-induced core transcription factor (SNAIL1, ZEB1 and Twist1) and mesenchymal gene (FN1 and VIM) expression.ConclusionsThese data indicate that NF-κB/RelA controls a SMAD-independent gene network whose regulation is required for initiation of Type II EMT. Type II EMT dramatically affects the induction and kinetics of TNF-dependent gene networks.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1707-x) contains supplementary material, which is available to authorized users.

Although the techniques Traditional Pearl Growing and Comprehensive Pearl Growing are believed to be useful for locating research evidence in any field, it may be particularly important for interdisciplinary topics where the use of effective controlled vocabulary plays a greater role in bringing together evidence that may be scattered across databases.

There is growing consensus about the factors critical for development and productivity of multidisciplinary teams, but few studies have evaluated their longitudinal changes. We present a longitudinal study of 10 multidisciplinary translational teams (MTTs), based on team process and outcome measures, evaluated before and after 3 years of CTSA collaboration. Using a mixed methods approach, an expert panel of five judges (familiar with the progress of the teams) independently rated team performance based on four process and four outcome measures, and achieved a rating consensus. Although all teams made progress in translational domains, other process and outcome measures were highly variable. The trajectory profiles identified four categories of team performance. Objective bibliometric analysis of CTSA-supported MTTs with positive growth in process scores showed that these teams tended to have enhanced scientific outcomes and published in new scientific domains, indicating the conduct of innovative science. Case exemplars revealed that MTTs that experienced growth in both process and outcome evaluative criteria also experienced greater innovation, defined as publications in different areas of science. Of the eight evaluative criteria, leadership-related behaviors were the most resistant to the interventions introduced. Well-managed MTTs demonstrate objective productivity and facilitate innovation.