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Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway
BACKGROUND: Obesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953623/ https://www.ncbi.nlm.nih.gov/pubmed/33712067 http://dx.doi.org/10.1186/s13287-021-02250-8 |
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author | Xu, Haoying Yang, Yanlei Fan, Linyuan Deng, Luchan Fan, Junfen Li, Di Li, Hongling Zhao, Robert Chunhua |
author_facet | Xu, Haoying Yang, Yanlei Fan, Linyuan Deng, Luchan Fan, Junfen Li, Di Li, Hongling Zhao, Robert Chunhua |
author_sort | Xu, Haoying |
collection | PubMed |
description | BACKGROUND: Obesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and differentiation. The objective of the present study was to identify and investigate the function and regulatory mechanism of lncRNAs on adipogenic differentiation of hADSCs. METHODS: We used lncRNA arrays to identify the prominent differentially expressed lncRNAs before and after hADSC adipogenic differentiation and verified their biological function through antisense oligonucleotide knockdown or lentivirus overexpression. The adipogenic differentiation of hADSCs was assessed by oil red O staining as well as the mRNA and protein levels of adipogenic marker genes through qRT-PCR and western blot. Bioinformatic tool LncPro and immunofluorescence was performed to uncover the interaction between lnc13728 and ZBED3. WNT/β-catenin signaling pathway was evaluated by western blot and immunofluorescence. RESULTS: The lncRNA arrays showed that lnc13728 expression was significantly upregulated after hADSC adipogenic differentiation and was correlated positively with the expression of the adipogenesis-related genes in human adipose tissue. Lnc13728 knockdown in hADSCs suppressed the expression of the adipogenesis-related genes at both mRNA and protein level and weakened lipid droplet production. Accordingly, lnc13728 overexpression enhanced hADSC adipogenic differentiation. Beyond that, lnc13728 co-localized with ZBED3 in the cytoplasm and regulated its expression positively. Downregulating ZBED3 had a negative effect on adipogenic differentiation, while the expression of WNT/β-catenin signaling pathway-related proteins was upregulated. CONCLUSIONS: Lnc13728 promotes hADSC adipogenic differentiation possibly by positively regulating the expression of ZBED3 which plays a role in inhibiting the WNT/β-catenin pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02250-8. |
format | Online Article Text |
id | pubmed-7953623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79536232021-03-12 Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway Xu, Haoying Yang, Yanlei Fan, Linyuan Deng, Luchan Fan, Junfen Li, Di Li, Hongling Zhao, Robert Chunhua Stem Cell Res Ther Research BACKGROUND: Obesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and differentiation. The objective of the present study was to identify and investigate the function and regulatory mechanism of lncRNAs on adipogenic differentiation of hADSCs. METHODS: We used lncRNA arrays to identify the prominent differentially expressed lncRNAs before and after hADSC adipogenic differentiation and verified their biological function through antisense oligonucleotide knockdown or lentivirus overexpression. The adipogenic differentiation of hADSCs was assessed by oil red O staining as well as the mRNA and protein levels of adipogenic marker genes through qRT-PCR and western blot. Bioinformatic tool LncPro and immunofluorescence was performed to uncover the interaction between lnc13728 and ZBED3. WNT/β-catenin signaling pathway was evaluated by western blot and immunofluorescence. RESULTS: The lncRNA arrays showed that lnc13728 expression was significantly upregulated after hADSC adipogenic differentiation and was correlated positively with the expression of the adipogenesis-related genes in human adipose tissue. Lnc13728 knockdown in hADSCs suppressed the expression of the adipogenesis-related genes at both mRNA and protein level and weakened lipid droplet production. Accordingly, lnc13728 overexpression enhanced hADSC adipogenic differentiation. Beyond that, lnc13728 co-localized with ZBED3 in the cytoplasm and regulated its expression positively. Downregulating ZBED3 had a negative effect on adipogenic differentiation, while the expression of WNT/β-catenin signaling pathway-related proteins was upregulated. CONCLUSIONS: Lnc13728 promotes hADSC adipogenic differentiation possibly by positively regulating the expression of ZBED3 which plays a role in inhibiting the WNT/β-catenin pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02250-8. BioMed Central 2021-03-12 /pmc/articles/PMC7953623/ /pubmed/33712067 http://dx.doi.org/10.1186/s13287-021-02250-8 Text en © The Author(s) 2021 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xu, Haoying Yang, Yanlei Fan, Linyuan Deng, Luchan Fan, Junfen Li, Di Li, Hongling Zhao, Robert Chunhua Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title | Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title_full | Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title_fullStr | Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title_full_unstemmed | Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title_short | Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway |
title_sort | lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of zbed3 and downregulation of the wnt/β-catenin pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953623/ https://www.ncbi.nlm.nih.gov/pubmed/33712067 http://dx.doi.org/10.1186/s13287-021-02250-8 |
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