title: Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage.
abstract: Vascular smooth muscle cells (VSMCs) derived from cardiovascular progenitor cell (CVPC) lineage populate the tunica media of the aortic root. Understanding differentiation of VSMCs from CVPC will further our understanding of the molecular mechanisms contributing to aortic root aneurysms, and thus, facilitate the development of novel therapeutic agents to prevent this devastating complication. It is established that the yes-associated protein (YAP) and Hippo pathway is important for VSMC proliferation and phenotype switch. To determine the role of YAP in differentiation of VSMCs from CVPCs, we utilized the in vitro monolayer lineage specific differentiation method by differentiating human embryonic stem cells into CVPCs, and then, into VSMCs. We found that expression of YAP decreased during differentiation of VSMC from CVPCs. Overexpression of YAP attenuated expression of VSMC contractile markers and impaired VSMC function. Knockdown of YAP increased expression of contractile proteins during CVPC-VSMCs differentiation. Importantly, expression of YAP decreased transcription of myocardin during this process. Overexpression of YAP in PAC1 SMC cell line inhibited luciferase activity of myocardin proximal promoter in a dose dependent and NKX2.5 dependent manners. YAP protein interacted with NKX2.5 protein and inhibited binding of NKX2.5 to the 5'-proximal promoter region of myocardin in CVPC-derived VSMCs. In conclusion, YAP negatively regulates differentiation of VSMCs from CVPCs by decreasing transcription of myocardin in a NKX2.5-dependent manner. Stem Cells 2017;35:351-361.
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.|Department of Vascular Surgery, Xiangya School of medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Lunchang
authors: L
authors: Wang
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Ping
authors: P
authors: Qiu
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Jiao
authors: J
authors: Jiao
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Hiroyuki
authors: H
authors: Hirai
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Wei
authors: W
authors: Xiong
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Jifeng
authors: J
authors: Zhang
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Tianqing
authors: T
authors: Zhu
authors: Biologic and Materials Sciences, Biomedical Engineering, Macromolecular Science and Engineering, Materials Science and Engineering, University of Michigan, Ann arbor, Michigan, USA.
authors: Peter X
authors: PX
authors: Ma
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Y Eugene
authors: YE
authors: Chen
authors: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, Michigan, USA.
authors: Bo
authors: B
authors: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019070:Cell Lineage; D055785:Gene Knockdown Techniques; D000072576:Homeobox Protein Nkx-2.5 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D000091102:YAP-Signaling Proteins; D000099251:Myocardin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D000072576:Homeobox Protein Nkx-2.5; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D000099251:Myocardin; C095552:NKX2-5 protein, human; C088374:YAP1 protein, human
keywords: Cardiovascular progenitor cell; Differentiation; Stem cells; Vascular smooth muscle cell; Yes-associated protein