Transcription Factors In Lung Research Articles

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Effect of Cigarette Smoke on the Activation of Transcription Factors in Mouse Lung

The effect of cigarette smoke on in vitro and in vivo transcription factor activation in the lung was examined. We first examined if NF-κB is activated by cigarette smoke condensate (CSC) in vitro. Using two different lung cell lines (H1299 and H-838), we did not observe activation of NF-κB following CSC exposure. We next examined if cigarette smoke could activate NF-κB in vivo. Mice were exposed to cigarette smoke for 1, 2, 3, or 6 hr, and 2, 5, 10, 15, 20, 42, or 56 days (6 hr/day, 5 days/wk). For all times except 20 and 42 days, the DNA binding activity of NF-κB in the lung and liver was either not changed or decreased by exposure to cigarette smoke. For the 20- and 42-day time points, the DNA binding activity in the lung was slightly increased. We also examined two other transcription factors: AP-1 and hypoxia inducible factor (HIF). Similar to NF-κB, the DNA binding activity of AP-1 and HIF was slightly elevated at 42 days but decreased at 56 days. These studies show that cigarette smoke does not activate NF-κB, AP-1 or HIF in the lung. Cigarette smoke activation of other transcription factors in the lung is currently being studied. (Supported by Kentucky Lung Cancer Research Program)

Alpha-melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion.

Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock or visceral or renal ischemia. Alpha-melanocyte-stimulating hormone (alpha-MSH) is an antiinflammatory cytokine, which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if alpha-MSH inhibits acute lung injury after renal ischemia and to determine the early mechanisms of alpha-MSH action. Mice were subjected to renal ischemia treated with vehicle or alpha-MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for intracellular adhesion molecule-1 and tumor necrosis factor-alpha. Renal ischemia rapidly activated kidney and lung nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury. Alpha-MSH administration immediately before reperfusion significantly decreased kidney and lung injury and prevented activation of kidney and lung transcription factors and stress response genes, and lung intracellular adhesion molecule-1 and tumor necrosis factor-alpha at early time points after renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after renal ischemia. alpha-MSH protects against both kidney and lung damage after renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury.

Upregulation of transcription factors in lung in the early phase of postpneumonectomy lung growth.

In the adult rodent, pneumonectomy results in compensatory lung growth characterized by cell proliferation. The molecular mechanisms governing this response remain unknown. We hypothesized that, in the early period postpneumonectomy, upregulated expression of transcription factors drives the growth process. We utilized a cDNA expression array to screen for upregulated transcription factors after left pneumonectomy in adult C57BL/6 mice, using unoperated mice as controls. Quantification of mRNA expression in the remaining lung at 2 h demonstrated a twofold or greater upregulation of six transcription factors: early growth response gene-1 (Egr-1), Nurr77, tristetraprolin, the primary inhibitor of nuclear factor-kappa B (I kappa B-alpha), gut-enriched Krüppel-like factor (GKLF), and LRG-21. Northern analysis was used to quantify the upregulation of expression of these genes relative to sham thoracotomy and unoperated controls. The largest increase was in Egr-1 (4.7-fold > naive). Time-course analysis over the first 24 h confirmed the transient nature of the early upregulation. In the context that postpneumonectomy lung growth is associated with cell proliferation and that genes such as Egr-1, Nurr77, LRG-21, and tristetraprolin have known roles in stress response, vascular biology, embryology, and cellular development, these data support the concept that transcription factors function early in the cascade of events leading to the compensatory response.