title: Sevoflurane represses the self-renewal ability by regulating miR-7a,7b/Klf4 signalling pathway in mouse embryonic stem cells.
abstract: Sevoflurane is a frequently-used clinical inhalational anaesthetic and can cause toxicity to embryos during foetal development. Embryonic stem cells (ESCs) are derived from the inner cell mass of blastospheres and can be used as a useful model of early development. Here, we found that sevoflurane significantly influenced self-renewal ability of mESCs on stemness maintenance and cell proliferation. The cell cycle was arrested via G1 phase delay. We further found that sevoflurane upregulated expression of miR-7a,7b to repress self-renewal. Next we performed rescue experiments and found that after adding miR-7a,7b inhibitor into mESCs treated with sevoflurane, its influence on self-renewal could be blocked. Further we identified stemness factor Klf4 as the direct target of miR-7a,7b. Overexpression of Klf4 restored self-renewal ability repressed by miR-7a,7b or sevoflurane. In this work, we determined that sevoflurane repressed self-renewal ability by regulating the miR-7a,7b/Klf4 signalling pathway in mESCs. Our study demonstrated molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on safe usage of inhalational anaesthetic during non-obstetric surgery.
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Guifeng
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Nai
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Longqiu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Hospital Infections, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Hospital Infections, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China. doctorsq@126.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Song
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000066450:Mouse Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C549243:MIRN7 microRNA, mouse; D008738:Methyl Ethers; D035683:MicroRNAs; D000077149:Sevoflurane