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Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells

Unregulated activity of myofibroblasts, highly contractile cells that deposit abundant extracellular matrix (ECM), leads to fibrosis. To study the modulation of myofibroblast activity, we used human adipose-derived mesenchymal stem cells (ADSCs), which have much potential in regenerative medicine. W...

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Detalles Bibliográficos
Autores principales: Desai, Vivek D., Hsia, Henry C., Schwarzbauer, Jean E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900664/
https://www.ncbi.nlm.nih.gov/pubmed/24466271
http://dx.doi.org/10.1371/journal.pone.0086865
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author Desai, Vivek D.
Hsia, Henry C.
Schwarzbauer, Jean E.
author_facet Desai, Vivek D.
Hsia, Henry C.
Schwarzbauer, Jean E.
author_sort Desai, Vivek D.
collection PubMed
description Unregulated activity of myofibroblasts, highly contractile cells that deposit abundant extracellular matrix (ECM), leads to fibrosis. To study the modulation of myofibroblast activity, we used human adipose-derived mesenchymal stem cells (ADSCs), which have much potential in regenerative medicine. We found that ADSCs treated with TGF-β developed a myofibroblastic phenotype with increases in α-smooth muscle actin (α-SMA), a myofibroblast marker, and ECM proteins type I collagen and fibronectin. In contrast, treatment with bFGF had the opposite effect. bFGF-differentiated ADSCs showed marked down-regulation of α-SMA expression, collagen I, and fibronectin, and loss of focal adhesions and stress fibers. Functionally, bFGF-differentiated ADSCs were significantly more migratory, which correlated with up-regulation of tenascin-C, an anti-adhesive ECM protein, and vimentin, a pro-migratory cytoskeletal protein. On the other hand, TGF-β-differentiated ADSCs were significantly more contractile than bFGF-differentiated cells. Interestingly, cells completely reversed their morphologies, marker expression, signaling pathways, and contractility versus migratory profiles when switched from culture with one growth factor to the other, demonstrating that the myofibroblast differentiation process is not terminal. Cell differentiation was associated with activation of Smad2 downstream of TGF-β and of ERK/MAP kinase downstream of bFGF. Reversibility of the TGF-β-induced myofibroblastic phenotype depends, in part, on bFGF-induced ERK/MAP kinase signaling. These findings show that ADSC differentiation into myofibroblasts and re-differentiation into fibroblast-like cells can be manipulated with growth factors, which may have implications in the development of novel therapeutic strategies to reduce the risk of fibrosis.
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spelling pubmed-39006642014-01-24 Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells Desai, Vivek D. Hsia, Henry C. Schwarzbauer, Jean E. PLoS One Research Article Unregulated activity of myofibroblasts, highly contractile cells that deposit abundant extracellular matrix (ECM), leads to fibrosis. To study the modulation of myofibroblast activity, we used human adipose-derived mesenchymal stem cells (ADSCs), which have much potential in regenerative medicine. We found that ADSCs treated with TGF-β developed a myofibroblastic phenotype with increases in α-smooth muscle actin (α-SMA), a myofibroblast marker, and ECM proteins type I collagen and fibronectin. In contrast, treatment with bFGF had the opposite effect. bFGF-differentiated ADSCs showed marked down-regulation of α-SMA expression, collagen I, and fibronectin, and loss of focal adhesions and stress fibers. Functionally, bFGF-differentiated ADSCs were significantly more migratory, which correlated with up-regulation of tenascin-C, an anti-adhesive ECM protein, and vimentin, a pro-migratory cytoskeletal protein. On the other hand, TGF-β-differentiated ADSCs were significantly more contractile than bFGF-differentiated cells. Interestingly, cells completely reversed their morphologies, marker expression, signaling pathways, and contractility versus migratory profiles when switched from culture with one growth factor to the other, demonstrating that the myofibroblast differentiation process is not terminal. Cell differentiation was associated with activation of Smad2 downstream of TGF-β and of ERK/MAP kinase downstream of bFGF. Reversibility of the TGF-β-induced myofibroblastic phenotype depends, in part, on bFGF-induced ERK/MAP kinase signaling. These findings show that ADSC differentiation into myofibroblasts and re-differentiation into fibroblast-like cells can be manipulated with growth factors, which may have implications in the development of novel therapeutic strategies to reduce the risk of fibrosis. Public Library of Science 2014-01-23 /pmc/articles/PMC3900664/ /pubmed/24466271 http://dx.doi.org/10.1371/journal.pone.0086865 Text en © 2014 Desai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Desai, Vivek D.
Hsia, Henry C.
Schwarzbauer, Jean E.
Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title_full Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title_fullStr Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title_full_unstemmed Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title_short Reversible Modulation of Myofibroblast Differentiation in Adipose-Derived Mesenchymal Stem Cells
title_sort reversible modulation of myofibroblast differentiation in adipose-derived mesenchymal stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900664/
https://www.ncbi.nlm.nih.gov/pubmed/24466271
http://dx.doi.org/10.1371/journal.pone.0086865
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