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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Actin Cytoskeleton, Actins, Active Transport, Cell Nucleus, Animals, Blotting, Western, Carotid Artery Injuries, Carotid Artery, Common, Cell Differentiation, Coronary Vessels, DNA-Binding Proteins, Disease Models, Animal, Enzyme Activation, Gene Expression Regulation, Gene Knockdown Techniques, Genotype, HEK293 Cells, Humans, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 14, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Myosin Heavy Chains, Nuclear Proteins, Oncogene Proteins, Fusion, Phenotype, Phosphorylation, Protein Kinase Inhibitors, RNA Interference, Serum Response Factor, Signal Transduction, Time Factors, Trans-Activators, Transfection, Vasoconstriction, rhoA GTP-Binding Protein.
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Is mitogen-activated protein kinase 14 a novel negative regulatory switch for the vascular smooth muscle cell contractile gene program? Context: Several studies have shown through chemical inhibitors that p38 mitogen-activated protein kinase (MAPK) promotes vascular smooth muscle cell (VSMC) differentiation. Here, we evaluate the effects of knocking down a dominant p38MAPK isoform on VSMC differentiation. Knockdown of p38MAPKα (MAPK14) in human coronary artery SMCs unexpectedly increases VSMC differentiation genes, such as miR145, ACTA2, CNN1, LMOD1, and TAGLN, with little change in the expression of serum response factor (SRF) and 2 SRF cofactors, myocardin (MYOCD) and myocardin-related transcription factor A (MKL1). A variety of chemical and biological inhibitors demonstrate a critical role for a RhoA-MKL1-SRF-dependent pathway in mediating these effects. MAPK14 knockdown promotes MKL1 nuclear localization and VSMC marker expression, an effect partially reversed with Y27632; in contrast, MAP2K6 (MKK6) blocks MKL1 nuclear import and VSMC marker expression. Immunostaining and Western blotting of injured mouse carotid arteries reveal elevated MAPK14 (both total and phosphorylated) and reduced VSMC marker expression.
assistant
Reduced MAPK14 expression evokes unanticipated increases in VSMC contractile genes, suggesting an unrecognized negative regulatory role for MAPK14 signaling in VSMC differentiation. Final Decision: yes