β-catenin-coordinated lncRNA MALAT1 up-regulation of ZEB-1 could enhance the telomerase activity in HGF-mediated differentiation of bone marrow mesenchymal stem cells into hepatocytes
To investigate role of β-catenin and lncRNA MALAT1/miR-217 axis to converge into the regulation of ZEB-1 in hepatocyte growth factor (HGF)-induced hepatocytes differentiated from bone marrow mesenchymal stem cells (BM-MSCs). BM-MSCs were isolated and HGF was used to induce the differentiation of BM-...
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Published in | Pathology, research and practice Vol. 215; no. 3; pp. 546 - 554 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Elsevier GmbH
01.03.2019
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Subjects | |
Online Access | Get full text |
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Summary: | To investigate role of β-catenin and lncRNA MALAT1/miR-217 axis to converge into the regulation of ZEB-1 in hepatocyte growth factor (HGF)-induced hepatocytes differentiated from bone marrow mesenchymal stem cells (BM-MSCs).
BM-MSCs were isolated and HGF was used to induce the differentiation of BM-MSCs into hepatocytes. HSC-T6 cells, BRL-3 A cells and differentiated BM-MSCs were treated by lipopolysaccharide(LPS). shRNAs were used to silence β-catenin and recombinant plasmids were used to over-express ZEB1. Measurement of cell viability was conducted using MTT assay and Hoechst 33342 staining. RNA immunoprecipitation (RIP) assay was used to determine binding of miR-217-3p and MALAT1.
BM-MSCs successfully differentiated into hepatocytes by HGF treatment. Expression of β-catenin, ZEB-1 and TERT was up-regulated to a higher level in hepatocytes differentiated from BM-MSCs than HSC-T6 cells and BRL-3 A cells after LPS stimulation. When β-catenin was knocked down in all cell lines, expression of β-catenin, ZEB-1 and TERT was significantly decreased as well as telomerase activity. While when ZEB1 was over-expressed, expression of TERT and telomerase activity was all significantly up-regulated. In hepatocytes differentiated from BM-MSCs, miR-217 was down-regulated and lncRNA MALAT1 was up-regulated. RIP analysis showed MALAT1 was physically associated with miR-217 and might function in the regulation of ZEB-1, further enhancing the expression of TERT so as to augment telomerase activity.
We successfully used HGF to mediate differentiation of BM-MSCs into hepatocytes, and found that β-catenin-coordinated MALAT1/miR-217 axis could up-regulate expression of ZEB-1 and further enhanced the telomerase activity through regulation of TERT in BM-MSCs differentiating into hepatocytes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0344-0338 1618-0631 |
DOI: | 10.1016/j.prp.2019.01.002 |