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- Publisher Website: 10.1164/rccm.200507-1058OC
- Scopus: eid_2-s2.0-30344485686
- PMID: 16179636
- WOS: WOS:000234520400018
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Article: Negative regulation of myofibroblast differentiation by PTEN (phosphatase and tensin homolog deleted on chromosome 10)
Title | Negative regulation of myofibroblast differentiation by PTEN (phosphatase and tensin homolog deleted on chromosome 10) |
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Authors | |
Keywords | Fibrosis Smooth muscle actin PTEN Myofibroblast Phosphatase |
Issue Date | 2006 |
Citation | American Journal of Respiratory and Critical Care Medicine, 2006, v. 173, n. 1, p. 112-121 How to Cite? |
Abstract | Rationale: Myofibroblasts are primary effector cells in idiopathic pulmonary fibrosis (IPF). Defining mechanisms of myofibroblast differentiation may be critical to the development of novel therapeutic agents. Objective: To show that myofibroblast differentiation is regulated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity in vivo, and to identify a potential mechanism by which this occurs. Methods: We used tissue sections of surgical lung biopsies from patients with IPF to localize expression of PTEN and α-smooth muscle actin (α-SMA). We used cell culture of pten -/- and wild-type fibroblasts, as well as adenoviral strategies and pharmacologic inhibitors, to determine the mechanism by which PTEN inhibits α-SMA, fibroblast proliferation, and collagen production. Results: In human lung specimens of IPF, myofibroblasts within fibroblastic foci demonstrated diminished PTEN expression. Furthermore, inhibition of PTEN in mice worsened bleomycin-induced fibrosis. In pten-/- fibroblasts, and in normal fibroblasts in which PTEN was inhibited, α-SMA, proliferation, and collagen production was upregulated. Addition of transforming growth factor-β to wild-type cells, but not pten-/- cells, resulted in increased α-SMA expression in a time-dependent fashion. In pten -/- cells, reconstitution of PTEN decreased α-SMA expression, proliferation, and collagen production, whereas overexpression of PTEN in wild-type cells inhibited transforming growth factor-β-induced myofibroblast differentiation. It was observed that both the protein and lipid phosphatase actions of PTEN were capable of modulating the myofibroblast phenotype. Conclusions: The results indicate that in IPF, myofibroblasts have diminished PTEN expression. Inhibition of PTEN in vivo promotes fibrosis, and PTEN inhibits myofibroblast differentiation in vitro. |
Persistent Identifier | http://hdl.handle.net/10722/292555 |
ISSN | 2023 Impact Factor: 19.3 2023 SCImago Journal Rankings: 5.336 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | White, Eric S. | - |
dc.contributor.author | Atrasz, Rachelle G. | - |
dc.contributor.author | Hu, Biao | - |
dc.contributor.author | Phan, Sem H. | - |
dc.contributor.author | Stambolic, Vuk | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Hogaboam, Cory M. | - |
dc.contributor.author | Flaherty, Kevin R. | - |
dc.contributor.author | Martinez, Fernando J. | - |
dc.contributor.author | Kontos, Christopher D. | - |
dc.contributor.author | Toews, Galen B. | - |
dc.date.accessioned | 2020-11-17T14:56:44Z | - |
dc.date.available | 2020-11-17T14:56:44Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | American Journal of Respiratory and Critical Care Medicine, 2006, v. 173, n. 1, p. 112-121 | - |
dc.identifier.issn | 1073-449X | - |
dc.identifier.uri | http://hdl.handle.net/10722/292555 | - |
dc.description.abstract | Rationale: Myofibroblasts are primary effector cells in idiopathic pulmonary fibrosis (IPF). Defining mechanisms of myofibroblast differentiation may be critical to the development of novel therapeutic agents. Objective: To show that myofibroblast differentiation is regulated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity in vivo, and to identify a potential mechanism by which this occurs. Methods: We used tissue sections of surgical lung biopsies from patients with IPF to localize expression of PTEN and α-smooth muscle actin (α-SMA). We used cell culture of pten -/- and wild-type fibroblasts, as well as adenoviral strategies and pharmacologic inhibitors, to determine the mechanism by which PTEN inhibits α-SMA, fibroblast proliferation, and collagen production. Results: In human lung specimens of IPF, myofibroblasts within fibroblastic foci demonstrated diminished PTEN expression. Furthermore, inhibition of PTEN in mice worsened bleomycin-induced fibrosis. In pten-/- fibroblasts, and in normal fibroblasts in which PTEN was inhibited, α-SMA, proliferation, and collagen production was upregulated. Addition of transforming growth factor-β to wild-type cells, but not pten-/- cells, resulted in increased α-SMA expression in a time-dependent fashion. In pten -/- cells, reconstitution of PTEN decreased α-SMA expression, proliferation, and collagen production, whereas overexpression of PTEN in wild-type cells inhibited transforming growth factor-β-induced myofibroblast differentiation. It was observed that both the protein and lipid phosphatase actions of PTEN were capable of modulating the myofibroblast phenotype. Conclusions: The results indicate that in IPF, myofibroblasts have diminished PTEN expression. Inhibition of PTEN in vivo promotes fibrosis, and PTEN inhibits myofibroblast differentiation in vitro. | - |
dc.language | eng | - |
dc.relation.ispartof | American Journal of Respiratory and Critical Care Medicine | - |
dc.subject | Fibrosis | - |
dc.subject | Smooth muscle actin | - |
dc.subject | PTEN | - |
dc.subject | Myofibroblast | - |
dc.subject | Phosphatase | - |
dc.title | Negative regulation of myofibroblast differentiation by PTEN (phosphatase and tensin homolog deleted on chromosome 10) | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1164/rccm.200507-1058OC | - |
dc.identifier.pmid | 16179636 | - |
dc.identifier.scopus | eid_2-s2.0-30344485686 | - |
dc.identifier.volume | 173 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 112 | - |
dc.identifier.epage | 121 | - |
dc.identifier.eissn | 1073-449X | - |
dc.identifier.isi | WOS:000234520400018 | - |
dc.identifier.issnl | 1073-449X | - |