title: Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells.
abstract: The miR-122 is a tissue-specific miRNA; its expression is abundant in liver. MiR-122 upregulation is crucial for differentiation, functionality, and maintenance of differentiated phenotype in hepatocytes. The improving effects of trichostatin A (TSA) on hepatic differentiation have been reported previously. The aim of this study was to determine whether TSA can affect the expression of miR-122 in hepatocyte-like cells (HLCs) generated from human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The hepatic differentiation of hAT-MSCs induced by a mixture of growth factors and cytokines either with or without TSA treatments. The functionality of HLCs generated with or without TSA and the expression levels of miR-122 were studied. The expression levels of miR-122 in TSA-treated HLCs was significantly (p < 0.05) higher than those generated by growth factors and cytokines, only. The downregulation of a-fetoprotein (AFP) levels but enhanced albumin synthesis (p < 0.05) and upregulation of liver-enriched transcription factors (LETFs) HNF4α (hepatocyte nuclear factor 4α) and HNF6 (hepatocyte nuclear factor 6) were observed in TSA-treated HLCs (p < 0.05). In conclusion, administration of TSA in hepatogenic differentiation of hAT-MSCs resulted in higher expression levels of miR-122, facilitation of differentiation, and subsequently attenuation of AFP levels.
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Effat
authors.initials: E
authors.lastname: Alizadeh
authors.affiliation: Department of Stem Cells and Developmental Biology at Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACER, Royan Institute, Tehran, I.R. Iran.
authors.forename: MohamadReza Baghaban
authors.initials: MB
authors.lastname: Eslaminejad
authors.affiliation: Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbarzadeh
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Zohre
authors.initials: Z
authors.lastname: Sadeghi
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Mozghan
authors.initials: M
authors.lastname: Abasi
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Herizchi
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.|The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Golgasht Ave., Tabriz 3137851656, I.R. Iran.
authors.forename: Nosratollah
authors.initials: N
authors.lastname: Zarghami
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D051559:Hepatocyte Nuclear Factor 6 / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D051559:Hepatocyte Nuclear Factor 6; D006877:Hydroxamic Acids; D035683:MicroRNAs; D000509:alpha-Fetoproteins; C012589:trichostatin A
keywords: HNF4a; HNF6; hepatocyte-like cells; mesenchymal stem cells; miR-122; trichostatin A; α-fetoprotein