Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by vascular remodeling and vasoconstriction, which is associated with increased intracellular calcium ion (Ca2+) concentration. Platelet-derived growth factor-BB (PDGF-BB) is the most potent mitogen for pulmonary arterial smooth muscle cells (PASMCs) and involved in vascular remodeling during PAH development. PDGF signaling has been proved to participate in maintaining Ca2+ homeostasis of PASMCs, however, the mechanism needs to be further elucidated. Here we illuminate that the expression of PMCA4 was downregulated in PASMCs after PDGF-BB stimulation, which was abolished by MEK/ERK inhibition. Functionally, suppression of PMCA4 attenuated the intracellular Ca2+ ([Ca2+]i) clearance in PASMCs after Ca2+ entry, promoting cell proliferation and elevating cells locomotion through mediating formation of focal adhesion. Additionally, the expression of PMCA4 was decreased in the pulmonary artery of MCT- or hypoxia-induced PAH rats. Moreover, knockdown of PMCA4 could increase the right ventricular systolic pressure and wall thickness of pulmonary artery in rats raised under normal condition. Taken together, our data proved the importance of the PDGF/MEK/ERK/PMCA4 axis in intracellular Ca2+ homeostasis in PASMCs, indicating a functional role of PMCA4 in pulmonary arterial remodeling and PAH development.
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PMID:PDGF/MEK/ERK Axis represses Ca2+ clearance via Decreasing the Abundance of Plasma Membrane Ca2+ Pump PMCA4 in Pulmonary Arterial Smooth Muscle Cells. 3296 25