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Full-Text Articles in Translational Medical Research
Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande
Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande
Center for Translational Medicine Faculty Papers
Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …
Apoptosis Signal-Regulating Kinase 1 Inhibition Attenuates Human Airway Smooth Muscle Growth And Migration In Chronic Obstructive Pulmonary Disease., Mathew S. Eapen, Anudeep Kota, Howard Vindin, Kielan D. Mcalinden, Dia Xenaki, Brian G. Oliver, Deepak A. Deshpande, Sukhwinder Singh Sohal, Pawan Sharma
Apoptosis Signal-Regulating Kinase 1 Inhibition Attenuates Human Airway Smooth Muscle Growth And Migration In Chronic Obstructive Pulmonary Disease., Mathew S. Eapen, Anudeep Kota, Howard Vindin, Kielan D. Mcalinden, Dia Xenaki, Brian G. Oliver, Deepak A. Deshpande, Sukhwinder Singh Sohal, Pawan Sharma
Center for Translational Medicine Faculty Papers
Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. …