title: Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately.
abstract: Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily.
authors.affiliation: College of Public Health, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China. Electronic address: mishua_@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: College of Public Health, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China. Electronic address: zhouren77@126.com.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhou
authors.affiliation: College of Public Health, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China. Electronic address: fy_575@sjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: College of Public Health, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China; Hongqiao International Institute of Medicine, School of Medicine, Shanghai Jiaotong University, 200336, PR China; Shanghai Ninth People's Hospital affiliated to Shanghai Jiaotong University, School of Medicine, PR China. Electronic address: wangyan@shsmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D051901:Smad4 Protein / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D019485:Bone Morphogenetic Proteins; D051901:Smad4 Protein; D012906:Smoke; D014028:Tobacco Smoke Pollution
keywords: Environment-gene-epigenetic interaction; Gata4; Heart development; Histone H3 acetylation; Low-dose effect; Mainstream smoke; Sidestream smoke