title: Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling.
abstract: Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling.
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jiao-Nin
authors.initials: JN
authors.lastname: Ning
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Guan-Song
authors.initials: GS
authors.lastname: Wang
authors.affiliation: Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Belguise
authors.affiliation: Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
authors.forename: Gui-Sheng
authors.initials: GS
authors.lastname: Qian
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Kai-Zhi
authors.initials: KZ
authors.lastname: Lu
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: yibin1974@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003135:Common Bile Duct; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008026:Ligation; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C556581:Smurf1 protein, rat; D044767:Ubiquitin-Protein Ligases
keywords: Bone morphogenic protein-2; Hepatopulmonary syndrome; Myogenic differentiation; Pulmonary microvascular endothelial cell