Role of Nrf2 signaling in development of hepatocyte-like cells.

IF 0.7 Q4 MEDICINE, RESEARCH & EXPERIMENTAL JOURNAL OF MEDICAL INVESTIGATION Pub Date : 2023-01-01 DOI:10.2152/jmi.70.343
Chie Takasu, Shuhai Chen, Luping Gao, Yu Saito, Yuji Morine, Tetsuya Ikemoto, Shinichiro Yamada, Mitsu Shimad
{"title":"Role of Nrf2 signaling in development of hepatocyte-like cells.","authors":"Chie Takasu, Shuhai Chen, Luping Gao, Yu Saito, Yuji Morine, Tetsuya Ikemoto, Shinichiro Yamada, Mitsu Shimad","doi":"10.2152/jmi.70.343","DOIUrl":null,"url":null,"abstract":"<p><p>Generation of hepatocytes from human adipose-derived mesenchymal stem cells (hADSCs) could be a promising alternative source of human hepatocytes. However, mechanisms to differentiate hepatocytes from hADSCs are not fully elucidated. We have previously demonstrated that our three-step differentiation protocol with glycogen synthase kinase (GSK) 3 inhibitor was effective to improve hepatocyte functions. In this study, we investigated the activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) on hADSCs undergoing differentiation to HLC (hepatocyte-like cells). Our three-step differentiation protocol was applied for 21 days (Step 1:day 1-6, Step2:day 6-11, Step3:day 11-21). Our results show that significant nuclear translocation of Nrf2 occurred from day 11 until the end of HLC differentiation. Nuclear translocation of Nrf2 and CYP3A4 activity in the GSK3 inhibitor-treated group was obviously higher than that in Activin A-treated groups at day 11. The maturation of HLCs was delayed in Nrf2-siRNA group compared to control group. Furthermore, CYP3A4 activity in Nrf2-siRNA group was decreased at the almost same level in Activin A-treated group. Nrf2 translocation might enhance the function of HLC and be a target for developing highly functional HLC. J. Med. Invest. 70 : 343-349, August, 2023.</p>","PeriodicalId":46910,"journal":{"name":"JOURNAL OF MEDICAL INVESTIGATION","volume":"70 3.4","pages":"343-349"},"PeriodicalIF":0.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOURNAL OF MEDICAL INVESTIGATION","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2152/jmi.70.343","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Generation of hepatocytes from human adipose-derived mesenchymal stem cells (hADSCs) could be a promising alternative source of human hepatocytes. However, mechanisms to differentiate hepatocytes from hADSCs are not fully elucidated. We have previously demonstrated that our three-step differentiation protocol with glycogen synthase kinase (GSK) 3 inhibitor was effective to improve hepatocyte functions. In this study, we investigated the activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) on hADSCs undergoing differentiation to HLC (hepatocyte-like cells). Our three-step differentiation protocol was applied for 21 days (Step 1:day 1-6, Step2:day 6-11, Step3:day 11-21). Our results show that significant nuclear translocation of Nrf2 occurred from day 11 until the end of HLC differentiation. Nuclear translocation of Nrf2 and CYP3A4 activity in the GSK3 inhibitor-treated group was obviously higher than that in Activin A-treated groups at day 11. The maturation of HLCs was delayed in Nrf2-siRNA group compared to control group. Furthermore, CYP3A4 activity in Nrf2-siRNA group was decreased at the almost same level in Activin A-treated group. Nrf2 translocation might enhance the function of HLC and be a target for developing highly functional HLC. J. Med. Invest. 70 : 343-349, August, 2023.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Nrf2信号传导在肝细胞样细胞发育中的作用。
从人脂肪来源的间充质干细胞(hADSCs)产生肝细胞可能是一种很有前途的人肝细胞替代来源。然而,从hADSCs分化肝细胞的机制尚未完全阐明。我们之前已经证明,我们的糖原合成酶激酶(GSK)3抑制剂的三步分化方案对改善肝细胞功能是有效的。在本研究中,我们研究了核因子红系2相关因子2(Nrf2)在分化为HLC(肝细胞样细胞)的hADSCs上的激活。我们的三步分化方案应用了21天(第1步:第1-6天,第2步:第6-11天,第3步:第11-21天)。我们的结果表明,从第11天到HLC分化结束,Nrf2发生了显著的核易位。在第11天,GSK3抑制剂处理组的Nrf2和CYP3A4活性的核转位明显高于激活素A处理组。与对照组相比,Nrf2-siRNA组的HLCs成熟延迟。此外,Nrf2-siRNA组的CYP3A4活性降低,与激活素A处理组几乎相同。Nrf2易位可能增强HLC的功能,并成为发展高功能HLC的靶点。J.Med.Invest。70:343-3492023年8月。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
JOURNAL OF MEDICAL INVESTIGATION
JOURNAL OF MEDICAL INVESTIGATION MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
1.20
自引率
0.00%
发文量
55
期刊最新文献
Changes in intestinal microbiota and biochemical parameters in patients with inflammatory bowel disease and irritable bowel syndrome induced by the prolonged addition of soluble fibers to usual drug therapy. Characterization of Outer Membrane Vesicles Produced by Vibrio vulnificus. Clarification of Psychiatric Nurses' Intentions and Analysis Contents in Observing Schizophrenia Patient. Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives. Feasibility of laparoscopic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumor with tumor diameter of >5 cm.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1