Functional interaction between PDGFβ and GluN2B-containing NMDA receptors in smooth muscle cell proliferation and migration in pulmonary arterial hypertension

• DOI: 10.1152/ajplung.00537.2017
• Publication Date: 2018-12-13T11:14:20Z
• Authors: Marceau Quatreden...; Morad K. Nakhleh; Sébastien J. Dumas; Audrey Courboulin; Maria C. Vinhas; Fabrice Antigny; Carole Phan; Christophe Guigna...; Imane Bendifallah; Matthieu Vocelle; Elie Fadel; Peter Dorfmüller; Marc Humbert; Sylvia Cohen-Kami...
• Keywords: Platelet-derived growth factor

In this study, we explored the complex interactions between platelet-derived growth factor (PDGF) and N-methyl-d-aspartate receptor (NMDAR) their effect on excessive proliferation migration of smooth muscle cells leading to obstructed arteries in pulmonary arterial hypertension (PAH). We report lower expression glutamate NMDA-type subunit 2B (GluN2B), a composing NMDARs expected affect cell survival/proliferation artery (PASMCs), PAH patient lungs. PASMC exposure PDGF-BB stimulated immediate increased levels phosphorylated Src family kinases (SFKs) together with GluN2B (its active form) surface relocalization, suggesting cross talk PDGFR-recruited SFKs NMDAR. Selective inhibition PDGFR-β or imatinib A-419259, respectively, one hand, specific small-interfering RNAs (siRNAs) other aborted PDGF-induced phosphorylation GluN2B, thus validating pathway. using Rö25-6981 silencing siRNA, presence PDGF-BB, significantly both PASMCs, strengthening functional importance Together, these results indicate that GluN2B-type NMDAR activation may confer PASMCs antiproliferative antimigratory properties. The decreased observed could mediate contributing medial hyperplasia development.