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Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration. Metformin(More)
TGF-β signaling is required for normal tissue repair; however, excessive TGF-β signaling can lead to robust profibrotic gene expression in fibroblasts, resulting in tissue fibrosis. TGF-β binds to cell-surface receptors, resulting in the phosphorylation of the Smad family of transcription factors to initiate gene expression. TGF-β also initiates(More)
The transfer of protective genes to the alveolar epithelium can attenuate lung injury if accomplished before its onset. The pathobiology of acute lung injury (ALI) includes formidable hurdles to gene transfer, including alveoli filled with fluid, inflammatory cells, and cytokines, all of which may impair gene transfer after the onset of injury. We tested(More)
Estrogen receptor-alpha (ERalpha) and its ligand estradiol (E2) has critical roles in breast cancer growth and are key therapeutic targets. In this study, we report a novel dual role of the adenosine A1 receptor (Adora1) as an E2/ERalpha target and a regulator of ERalpha transcriptional activity. In ERalpha-positive breast cancer cells, E2 upregulated(More)
Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac(More)
Laminins are heterotrimeric glycoproteins of the extracellular matrix that are secreted by epithelial cells and which are crucial for the normal structure and function of the basement membrane. We have generated a mouse harboring a conditional knockout of α3 laminin (Lama3(fl/fl)), one of the main laminin subunits in the lung basement membrane. At 60 days(More)
Laminins are heterotrimeric glycoproteins of the extracellular matrix that are secreted by epithelial cells and which are crucial for the normal structure and function of the basement membrane. We have generated a mouse harboring a conditional knockout of a3 laminin (Lama3 fl/fl), one of the main laminin subunits in the lung basement membrane. At 60 days(More)
Increased endothelial cell (EC) permeability and vascular inflammation along with alveolar epithelial damage are key features of acute lung injury (ALI). Products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC) showed protective effects against inflammatory signaling and vascular EC barrier dysfunction induced by(More)
Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in(More)
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