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Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)

Treatment for musculoskeletal fibromatosis remains challenging. Surgical excision for fibromatosis is the standard therapy but recurrence remains high. Corticosteroids, an anti-fibrogenic compound, have been used to treat early stage palmar fibromatosis, but the mechanism is unknown. We investigated...

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Autores principales: Wang, Jung-Pan, Yu, Hsiang-Hsuan Michael, Chiang, En-Rung, Wang, Jir-You, Chou, Po- Hsin, Hung, Shih-Chieh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019676/
https://www.ncbi.nlm.nih.gov/pubmed/29944666
http://dx.doi.org/10.1371/journal.pone.0198326
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author Wang, Jung-Pan
Yu, Hsiang-Hsuan Michael
Chiang, En-Rung
Wang, Jir-You
Chou, Po- Hsin
Hung, Shih-Chieh
author_facet Wang, Jung-Pan
Yu, Hsiang-Hsuan Michael
Chiang, En-Rung
Wang, Jir-You
Chou, Po- Hsin
Hung, Shih-Chieh
author_sort Wang, Jung-Pan
collection PubMed
description Treatment for musculoskeletal fibromatosis remains challenging. Surgical excision for fibromatosis is the standard therapy but recurrence remains high. Corticosteroids, an anti-fibrogenic compound, have been used to treat early stage palmar fibromatosis, but the mechanism is unknown. We investigated the inhibitory mechanism effect of corticosteroids in the murine model of fibromatosis nodule as well as in cultured FSCs. Quantitative reverse transcription/polymerase chain reaction (PCR) analysis and immunofluorescence (IF) staining for markers of myofibroblasts (α-smooth muscle actin and type III collagen) were used to examine the effect of dexamethasone on myofibroblasic differentiation of FSCs both in vitro and in vivo. Transforming growth factor-β1 (TGF-β1) signaling and its downstream targets were examined using western blot analysis. TGF-β1 expression in FSCs before and after dexamethasone treatment was compared. In addition, inhibition of TGF-β1 expression was examined using RNA interference (RNAi) on FSCs, both in vitro and in vivo. Treating FSCs with dexamethasone inhibited FSCs’ myofibroblastic differentiation in vitro. Treating FSCs with dexamethasone before or after implantation further inhibited formation of fibromatosis nodules. Dexamethasone suppressed expression of TGF-β1 and pSmad2/3 by FSCs in vitro. TGF-β1 knockdown FSCs showed reducing myofibroblastic differentiation both in vitro and in vivo. Finally, addition of TGF-β1 abolished dexamethasone-mediated inhibition of myofibroblastic differentiation. Dexamethasone inhibits the myofibroblastic differentiated potential of FSCs both in vitro and in vivo through inhibition of TGF-β1 expression in FSCs. TGF-β1 plays a key role in myofibroblastic differentiation.
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spelling pubmed-60196762018-07-07 Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1) Wang, Jung-Pan Yu, Hsiang-Hsuan Michael Chiang, En-Rung Wang, Jir-You Chou, Po- Hsin Hung, Shih-Chieh PLoS One Research Article Treatment for musculoskeletal fibromatosis remains challenging. Surgical excision for fibromatosis is the standard therapy but recurrence remains high. Corticosteroids, an anti-fibrogenic compound, have been used to treat early stage palmar fibromatosis, but the mechanism is unknown. We investigated the inhibitory mechanism effect of corticosteroids in the murine model of fibromatosis nodule as well as in cultured FSCs. Quantitative reverse transcription/polymerase chain reaction (PCR) analysis and immunofluorescence (IF) staining for markers of myofibroblasts (α-smooth muscle actin and type III collagen) were used to examine the effect of dexamethasone on myofibroblasic differentiation of FSCs both in vitro and in vivo. Transforming growth factor-β1 (TGF-β1) signaling and its downstream targets were examined using western blot analysis. TGF-β1 expression in FSCs before and after dexamethasone treatment was compared. In addition, inhibition of TGF-β1 expression was examined using RNA interference (RNAi) on FSCs, both in vitro and in vivo. Treating FSCs with dexamethasone inhibited FSCs’ myofibroblastic differentiation in vitro. Treating FSCs with dexamethasone before or after implantation further inhibited formation of fibromatosis nodules. Dexamethasone suppressed expression of TGF-β1 and pSmad2/3 by FSCs in vitro. TGF-β1 knockdown FSCs showed reducing myofibroblastic differentiation both in vitro and in vivo. Finally, addition of TGF-β1 abolished dexamethasone-mediated inhibition of myofibroblastic differentiation. Dexamethasone inhibits the myofibroblastic differentiated potential of FSCs both in vitro and in vivo through inhibition of TGF-β1 expression in FSCs. TGF-β1 plays a key role in myofibroblastic differentiation. Public Library of Science 2018-06-26 /pmc/articles/PMC6019676/ /pubmed/29944666 http://dx.doi.org/10.1371/journal.pone.0198326 Text en © 2018 Wang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Jung-Pan
Yu, Hsiang-Hsuan Michael
Chiang, En-Rung
Wang, Jir-You
Chou, Po- Hsin
Hung, Shih-Chieh
Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title_full Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title_fullStr Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title_full_unstemmed Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title_short Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)
title_sort corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (fscs) through downregulation of transforming growth factor-β1 (tgf-β1)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019676/
https://www.ncbi.nlm.nih.gov/pubmed/29944666
http://dx.doi.org/10.1371/journal.pone.0198326
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