title: The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling.
abstract: 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.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, College of Basic Medicine, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Department of Immunology, College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of clinical nursing, College of nursing, Harbin Medical University (Daqing), Daqing 163319, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology; D000068877:Imatinib Mesylate / Q000494:pharmacology; D047468:Immunoprecipitation; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism*; D016686:Monocrotaline / Q000494:pharmacology; D015260:Neprilysin / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D016686:Monocrotaline; D000068877:Imatinib Mesylate; D015260:Neprilysin
keywords: Endothelial-to-mesenchymal transition; Neprilysin; PDGF-B; Pulmonary artery remodeling; TGF-β1