研究动态
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纳米姜黄素在巨核细胞分化诱导中的经典NFκB通路参与

The Involvement of Canonical NFκB Pathway in Megakaryocyte Differentiation Induction by Nanocurcumin.

发表日期:2023 Jan 01
作者: Seyedeh Sahar Mortazavi Farsani, Dina Sadeghizadeh, Sadegh Babashah, Fariba Rad, Majid Sadeghizadeh
来源: Stem Cell Research & Therapy

摘要:

背景:巨核造血过程的特点是逐渐多倍体化和巨核细胞标志物的表达。许多转录因子和生理信号通路调控这一现象。我们之前的研究确定了纳米姜黄素药物通过诱导K562细胞系和造血干细胞巨核细胞分化。K562细胞是典型的慢性髓性白血病细胞,对凋亡具有抗性并表达bcr-abl融合基因。这些细胞有可能分化为红细胞和巨核细胞。姜黄素是一种以改变各种细胞中NFκB活性而著称的成分。NFκB途径调控多种基因,如凋亡和免疫反应基因。本研究旨在评估纳米姜黄素在K562细胞系中调控NFκB途径在巨核造血过程中的可能作用。 材料和方法:通过流式细胞术和显微镜成像检测纳米姜黄素处理的K562细胞中巨核细胞标志物的表达和表型改变,通过Western blot检测在不同时间纳米姜黄素诱导的巨核造血过程中K562细胞中NFκB的核内水平。通过定量RT-PCR分析不同时间纳米姜黄素处理的K562细胞中NFκB靶基因(c-MYC, BAX和NQO1)的表达。 结果:研究表明,在巨核细胞分化过程中,纳米姜黄素会短暂增加NFκB活性,随后导致c-MYC, BAX和NQO1靶基因表达的改变。 结论:NFκB途径可被认为是纳米姜黄素通过体外和体内巨核造血实验诱导巨核细胞分化的新途径。Copyright © 2023 Tehran University of Medical Sciences.
Background: Megakaryopoiesis is characterized by progressive polyploidization and the expression of megakaryocytic markers. Numerous transcription factors and physiological signaling pathways regulate this phenomenon. Megakaryocyte differentiation induction in the K562 cell line and hematopoietic stem cells via nanocurcumin drug has been identified in our previous study. K562 cells are typical Chronic Myelogenous Leukemia (CML) cells that are resistant to apoptosis and express the bcr-abl fusion gene. These cells have the potential to differentiate into erythrocytes and megakaryocytes. Curcumin is well known as a component with strong potential to alter NFκB activity in various cells. NFκB pathway regulates various genes such as apoptotic and immune response genes. The current study attempted to evaluate the possible role of nanocurcumin in NFκB pathway regulation during the megakaryopoiesis process in the K562 cell line. Materials and Methods: Megakaryocyte markers expression and phenotype alteration of nanocurcumin-treated K562 cells have been detected by flow cytometry and microscopy imaging. The nuclear level of the RelA (p65) subunit of NFκB was determined by western blot test in K562 cells during megakaryopoiesis induction via nanocurcumin treatment at different times. The expression of NFκB target genes including c-MYC, BAX, and NQO1 was also analyzed in nanocurcumin-treated K562 cells by quantitative RT-PCR assay at different times. Results: The study has shown that nanocurcumin causes an increase in NFκB activity transiently during megakaryocyte differentiation, followed by a change in the expression of c-MYC, BAX, and NQO1 target genes. Conclusion: The NFκB pathway can be considered a new pathway for inducing megakaryocyte differentiation by nanocurcumin in vitro and in vivo megakaryopoiesis experiments.Copyright © 2023 Tehran University of Medical Sciences.