Long noncoding RNA SNHG1 silencing accelerates hepatocyte-like cell differentiation of bone marrow-derived mesenchymal stem cells to alleviate cirrhosis <i>via</i> the microRNA-15a/SMURF1/UVRAG axis

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Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to attenuate cirrhosis. Long noncoding RNA (lncRNA) SNHG1 has been demonstrated to orchestrate BMSC differentiation, whereas its role in cirrhosis remains elusive. Therefore, this study was performed to figure out whether lncRNA SNHG1 was involved in cirrhosis by affecting HLC differentiation of BMSCs. Mouse BMSCs were isolated, and the BMSC differentiation into HLCs was induced by hepatocyte growth factor (HGF). A cirrhotic mouse model was established using carbon tetrachloride and phenobarbital, followed by intravenous injection of BMSCs with manipulated expression of lncRNA SNHG1, microRNA (miR)-15a, and SMURF1. Subsequent to HGF induction, expression of hepatocyte-related genes, albumin secretion, and glycogen accumulation was increased in BMSCs, suggesting the differentiation of BMSCs into HLCs. Mechanistically, lncRNA SNHG1 bound to miR-15a that targeted SMURF1, and SMURF1 diminished ATG5 and Wnt5a expression by enhancing the ubiquitination of UVRAG. LncRNA SNHG1 or SMURF1 silencing or miR-15a overexpression promoted differentiation of BMSCs into HLCs and repressed cirrhosis of mice by upregulating ATG5 and Wnt5a via UVRAG. Conclusively, lncRNA SNHG1 silencing might facilitate HLC differentiation from mouse BMSCs and alleviate cirrhosis via the miR-15a/SMURF1/UVRAG/ATG5/Wnt5a axis.

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Author and article information

Contributors

Feng Duan:

ORCID: http://orcid.org/0000-0002-8089-2963

duanfeng@vip.sina.com

Journal

Journal ID (nlm-ta): Cell Death Discov

Journal ID (iso-abbrev): Cell Death Discov

Title: Cell Death Discovery

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2058-7716

Publication date (Electronic): 22 February 2022

Publication date PMC-release: 22 February 2022

Publication date Collection: 2022

Volume: 8

Electronic Location Identifier: 77

Affiliations

[1 ]Shenzhen Beike Biotechnology Research Institute, Shenzhen, 518057 P.R. China

[2 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Intervention and Cell Therapy Center, , Shenzhen Hospital of Peking University, ; Shenzhen, 518057 P. R. China

[3 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Interventional Radiology, the First Medical Center, , Chinese PLA General Hospital, ; Beijing, 100853 P.R. China

[4 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Radiotherapy, the First Medical Center, , Chinese PLA General Hospital, ; Beijing, 100853 P.R. China

Author information

Feng Duan http://orcid.org/0000-0002-8089-2963

Article

Publisher ID: 850

DOI: 10.1038/s41420-022-00850-8

PMC ID: 8863836

PubMed ID: 35194023

SO-VID: c8e56763-ba8e-4b2b-a60b-0e7fd68d9d8f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 12 September 2021

Date revision received : 11 January 2022

Date accepted : 24 January 2022

Funding

Funded by: This study was funded by the outstanding project of the Chinese people’s liberation army (PLA) Medical Science and Technology Youth Cultivation Program (18QNP058).