Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells

被引:38
作者
Alizadeh, Effat [1 ]
Eslaminejad, MohamadReza Baghaban [2 ]
Akbarzadeh, Abolfazl [3 ]
Sadeghi, Zohre [1 ]
Abasi, Mozghan [1 ]
Herizchi, Roya [1 ]
Zarghami, Nosratollah [1 ,4 ]
机构
[1] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Biotechnol, Golgasht Ave, Tabriz 3137851656, Iran
[2] ACER, Royan Inst, Royan Inst Stem Cell Biol & Technol, Dept Stem Cells & Dev Biol,Cell Sci Res Ctr, Tehran, Iran
[3] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Nanotechnol, Golgasht Ave, Tabriz 3137851656, Iran
[4] Tabriz Univ Med Sci, Umbil Cord Stem Cell Res Ctr, Golgasht Ave, Tabriz 3137851656, Iran
关键词
hepatocyte-like cells; HNF4; alpha; HNF6; mesenchymal stem cells; miR-122; trichostatin A; alpha-fetoprotein; HEPATIC DIFFERENTIATION; IN-VITRO; ADIPOSE-TISSUE; ALPHA-FETOPROTEIN; MICRORNA-122; OVEREXPRESSION; EXPRESSION; THERAPY; HISTONE;
D O I
10.1111/cbdd.12664
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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) HNF4 alpha (hepatocyte nuclear factor 4 alpha) 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.
引用
收藏
页码:296 / 305
页数:10
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