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Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation
Hair follicle stem cells (HFSCs) are implicated in the formation of hair follicles and epidermis. This study aims to clarify the role of SMAD2 in regulating the differentiation of HFSCs, which is involved with Smurf2. Functional assays were carried out in human HFSCs to assess the effect of SMAD2 an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980066/ https://www.ncbi.nlm.nih.gov/pubmed/35379779 http://dx.doi.org/10.1038/s41420-022-00920-x |
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author | Lin, Bojie Huang, Dan Lin, Guanyu Miao, Yong Wang, Jin Fan, Zhexiang Hu, Zhiqi |
author_facet | Lin, Bojie Huang, Dan Lin, Guanyu Miao, Yong Wang, Jin Fan, Zhexiang Hu, Zhiqi |
author_sort | Lin, Bojie |
collection | PubMed |
description | Hair follicle stem cells (HFSCs) are implicated in the formation of hair follicles and epidermis. This study aims to clarify the role of SMAD2 in regulating the differentiation of HFSCs, which is involved with Smurf2. Functional assays were carried out in human HFSCs to assess the effect of SMAD2 and Smurf2 with altered expression on growth dynamics of HFSCs. Ubiquitination of SMAD2 and its protein stability were assessed. The binding relationship between NANOG and DNMT1 was assessed. A mouse skin wound model was induced to verify the effects of Smurf2/SMAD2/NANOG/DNMT1 on wound healing. SMAD2 overexpression was observed in HFSCs during differentiation and its ectopic expression contributed to promotion of differentiation and apoptosis of HFSCs while arresting cell proliferation. Mechanistic investigations indicated that Smurf2 promoted the ubiquitination and degradation of SMAD2, thus causing downregulation of SMAD2 expression. By this mechanism, NANOG expression was reduced and the subsequent DNMT1 transcriptional expression was also diminished, leading to suppression of differentiation and apoptosis of HFSCs while stimulating cell proliferation. Moreover, in vivo data showed that Smurf2 upregulation limited epidermal wound healing in mice by inhibiting the SMAD2/NANOG/DNMT1 axis. Our work proposed a potential target regarding SMAD2 restoration in promoting HFSC differentiation and skin wound healing. |
format | Online Article Text |
id | pubmed-8980066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89800662022-04-20 Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation Lin, Bojie Huang, Dan Lin, Guanyu Miao, Yong Wang, Jin Fan, Zhexiang Hu, Zhiqi Cell Death Discov Article Hair follicle stem cells (HFSCs) are implicated in the formation of hair follicles and epidermis. This study aims to clarify the role of SMAD2 in regulating the differentiation of HFSCs, which is involved with Smurf2. Functional assays were carried out in human HFSCs to assess the effect of SMAD2 and Smurf2 with altered expression on growth dynamics of HFSCs. Ubiquitination of SMAD2 and its protein stability were assessed. The binding relationship between NANOG and DNMT1 was assessed. A mouse skin wound model was induced to verify the effects of Smurf2/SMAD2/NANOG/DNMT1 on wound healing. SMAD2 overexpression was observed in HFSCs during differentiation and its ectopic expression contributed to promotion of differentiation and apoptosis of HFSCs while arresting cell proliferation. Mechanistic investigations indicated that Smurf2 promoted the ubiquitination and degradation of SMAD2, thus causing downregulation of SMAD2 expression. By this mechanism, NANOG expression was reduced and the subsequent DNMT1 transcriptional expression was also diminished, leading to suppression of differentiation and apoptosis of HFSCs while stimulating cell proliferation. Moreover, in vivo data showed that Smurf2 upregulation limited epidermal wound healing in mice by inhibiting the SMAD2/NANOG/DNMT1 axis. Our work proposed a potential target regarding SMAD2 restoration in promoting HFSC differentiation and skin wound healing. Nature Publishing Group UK 2022-04-04 /pmc/articles/PMC8980066/ /pubmed/35379779 http://dx.doi.org/10.1038/s41420-022-00920-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lin, Bojie Huang, Dan Lin, Guanyu Miao, Yong Wang, Jin Fan, Zhexiang Hu, Zhiqi Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title | Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title_full | Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title_fullStr | Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title_full_unstemmed | Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title_short | Smurf2-induced degradation of SMAD2 causes inhibition of hair follicle stem cell differentiation |
title_sort | smurf2-induced degradation of smad2 causes inhibition of hair follicle stem cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980066/ https://www.ncbi.nlm.nih.gov/pubmed/35379779 http://dx.doi.org/10.1038/s41420-022-00920-x |
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