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A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation
Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (MSC) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829670/ https://www.ncbi.nlm.nih.gov/pubmed/31578224 http://dx.doi.org/10.1083/jcb.201902022 |
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author | Guo, Ling Wang, Rong Zhang, Kuo Yuan, Jifan Wang, Jiaxin Wang, Xiaoxia Ma, Jianfei Wu, Chuanyue |
author_facet | Guo, Ling Wang, Rong Zhang, Kuo Yuan, Jifan Wang, Jiaxin Wang, Xiaoxia Ma, Jianfei Wu, Chuanyue |
author_sort | Guo, Ling |
collection | PubMed |
description | Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (MSC) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of PINCH-1 overrides signals from soft ECM and promotes OD. Finally, perturbation of either Smurf1 or BMPR2 expression is sufficient to block the effects of PINCH-1 on BMP signaling and MSC fate decision. Our findings delineate a key signaling mechanism through which mechano-environment controls BMPR2 level and MSC fate decision. |
format | Online Article Text |
id | pubmed-6829670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68296702020-05-04 A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation Guo, Ling Wang, Rong Zhang, Kuo Yuan, Jifan Wang, Jiaxin Wang, Xiaoxia Ma, Jianfei Wu, Chuanyue J Cell Biol Research Articles Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (MSC) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of PINCH-1 overrides signals from soft ECM and promotes OD. Finally, perturbation of either Smurf1 or BMPR2 expression is sufficient to block the effects of PINCH-1 on BMP signaling and MSC fate decision. Our findings delineate a key signaling mechanism through which mechano-environment controls BMPR2 level and MSC fate decision. Rockefeller University Press 2019-11-04 2019-10-02 /pmc/articles/PMC6829670/ /pubmed/31578224 http://dx.doi.org/10.1083/jcb.201902022 Text en © 2019 Guo et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Guo, Ling Wang, Rong Zhang, Kuo Yuan, Jifan Wang, Jiaxin Wang, Xiaoxia Ma, Jianfei Wu, Chuanyue A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title | A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title_full | A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title_fullStr | A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title_full_unstemmed | A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title_short | A PINCH-1–Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation |
title_sort | pinch-1–smurf1 signaling axis mediates mechano-regulation of bmpr2 and stem cell differentiation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829670/ https://www.ncbi.nlm.nih.gov/pubmed/31578224 http://dx.doi.org/10.1083/jcb.201902022 |
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