Home Blog of Signal Transduction Protein Tyrosine Kinase PDGFR The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

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The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

Endothelial-to-mesenchymal transition (EndoMT) has been recognized as a major reason for the pulmonary artery remodeling (PAR) in pulmonary artery hypertension (PAH). However, the molecular mechanisms and regulatory pathways involved in the EndoMT remain undefined. In the present study, we have confirmed that EndoMT was occurred in pulmonary arteries of rats induced by hypoxia and monocrotaline and in hypoxic pulmonary artery endothelial cells (PAECs). Moreover, hypoxia increased the expression of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) and decreased the expression of neprilysin (NEP), which contributed to the hypoxia-induced EndoMT of PAECs. Furthermore, a reciprocal regulation of PDGF-B and TGF-β1 induced by decreasing NEP promoted the EndoMT of PAECs under hypoxia, which was a novel molecular mechanism to reveal the EndoMT participating in PAR. More importantly, imatinib, a PDGF receptor antagonist, relieved PAR and EndoMT in PAH rats. Thus, our results identify a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease.

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