title: Progesterone signaling/miR-200a/zeb2 axis regulates self-renewal of mouse embryonic stem cells.
abstract: Progesterone is a steroid hormone and plays an important role during pregnancy. But the regulation mechanisms of progesterone-progesterone receptor (P4-PR) signaling during pregnancy remain largely unknown. In this study, we used medroxyprogesterone 17-acetate (MPA) which is a synthetic variant of progesterone and has 20-30 times the activity of progesterone to find that at the same physiological concentration as progesterone during early pregnancy MPA had no significant influence on ES cells self-renewal. But with the increasing of dosage, MPA can inhibit the self-renewal capacity of mouse embryonic stem cells (ES cells) and promote differentiation untimely. We further determined that MPA can influence the miR-200a/zeb2 pathway by down regulating the level of miR-200a. miR-200a significantly higher expressed in ES cells to down-regulate the expression of zeb2 to inhibit the self-renewal and promote differentiation of ES cells. Then we found that the function of MPA can be rescued by over-expression of miR-200a or down-regulation of zeb2. Our findings revealed the progesterone signaling/miR-200a/zeb2 axis regulating the progesterone signaling to insure the balance of self-renewal and differentiation of ES cells. Our study also provided new insight into the dosage of progesterone and it's derivant in the hormone replacement therapy for pregnant woman.
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200040 Shanghai, PR China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Ai
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 200092 Shanghai, PR China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200040 Shanghai, PR China.
authors.forename: Yanyi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200040 Shanghai, PR China; Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200040 Shanghai, PR China. Electronic address: tduan@yahoo.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D011374:Progesterone / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D012097:Repressor Proteins; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2; D011374:Progesterone; D017258:Medroxyprogesterone Acetate; D008156:Luciferases
keywords: Differentiation; Embryonic stem cells; Medroxyprogesterone 17-acetate; Progesterone; Self-renewal; Zeb2; miR-200a