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Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis
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| Zeitschriftentitel: | Journal of Cancer Research Updates |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Journal of Cancer Research Updates, 3, 2014, 1, S. 73-80 |
| Format: | E-Article |
| Sprache: | Unbestimmt |
| veröffentlicht: |
Neoplasia Research
|
| author_facet |
Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh |
|---|---|
| author |
Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh |
| spellingShingle |
Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh Journal of Cancer Research Updates Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| author_sort |
chao li |
| spelling |
Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh 1929-2279 Neoplasia Research http://dx.doi.org/10.6000/1929-2279.2014.03.01.8 <jats:p>Radiotherapy-induced fibrosis (RTIF) presents a challenge in radiotherapy for cancer patients. Although numerous studies have attempted to elucidate the mechanisms leading to RTIF, the pathogenesis of RTIF at the cellular and molecular level is still incompletely described. One key component involved in the post-radiation injury is the pleuripotent cytokine transforming growth factor (TGF)-β. TGF-β signaling pathway has been under intensive investigation about its critical role in radiation-induced fibroproliferative disease. Connective tissue growth factor (CTGF), also known as insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) is a potent regulator of fibroblast proliferation, cell adhesion, and stimulation of extracellular matrix production. CTGF is known as a major downstream mediator of the chronic fibrotic effects of TGF-β. Here we have demonstrated that irradiation and TGF-β induced CTGF, subsequently upregulates fibrotic factors such as fibronectin and type IV collagen. Furthermore, as HMG-CoA reductase inhibitors, statins inhibit expressions of CTGF and downstream fibrotic proteins in both normal human fetal fibroblasts (HFL-1) and human dermal fibroblasts (HDF) on TGF-β treatment or irradiation. Our study also demonstrates that simvastatin not only suppressed TGF-β-induced fibrosis through inhibition of CTGF production but also CTGF-induced fibrosis. We further show that simvastatin may act in a TGF-β-independent manner by inhibiting Rho kinase pathway. Taken together, these data suggest that radiotherapy may upregulate CTGF expression in a TGF-β-dependent and -independent manner, thereby enhancing expression of profibrotic factors and inducing lung fibrosis.</jats:p> Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis Journal of Cancer Research Updates |
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| title |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_unstemmed |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_full |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_fullStr |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_full_unstemmed |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_short |
Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_sort |
multiple mechanisms for anti-fibrotic functions of statins on radiotherapy induced fibrosis |
| url |
http://dx.doi.org/10.6000/1929-2279.2014.03.01.8 |
| publishDate |
2014 |
| physical |
73-80 |
| description |
<jats:p>Radiotherapy-induced fibrosis (RTIF) presents a challenge in radiotherapy for cancer patients. Although numerous studies have attempted to elucidate the mechanisms leading to RTIF, the pathogenesis of RTIF at the cellular and molecular level is still incompletely described. One key component involved in the post-radiation injury is the pleuripotent cytokine transforming growth factor (TGF)-β. TGF-β signaling pathway has been under intensive investigation about its critical role in radiation-induced fibroproliferative disease. Connective tissue growth factor (CTGF), also known as insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) is a potent regulator of fibroblast proliferation, cell adhesion, and stimulation of extracellular matrix production. CTGF is known as a major downstream mediator of the chronic fibrotic effects of TGF-β. Here we have demonstrated that irradiation and TGF-β induced CTGF, subsequently upregulates fibrotic factors such as fibronectin and type IV collagen. Furthermore, as HMG-CoA reductase inhibitors, statins inhibit expressions of CTGF and downstream fibrotic proteins in both normal human fetal fibroblasts (HFL-1) and human dermal fibroblasts (HDF) on TGF-β treatment or irradiation. Our study also demonstrates that simvastatin not only suppressed TGF-β-induced fibrosis through inhibition of CTGF production but also CTGF-induced fibrosis. We further show that simvastatin may act in a TGF-β-independent manner by inhibiting Rho kinase pathway. Taken together, these data suggest that radiotherapy may upregulate CTGF expression in a TGF-β-dependent and -independent manner, thereby enhancing expression of profibrotic factors and inducing lung fibrosis.</jats:p> |
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| author | Chao Li, Wei Li, Lathika Mohanraj, Qing Cai, Mitchell S. Anscher, Youngman Oh |
| author_facet | Chao Li, Wei Li, Lathika Mohanraj, Qing Cai, Mitchell S. Anscher, Youngman Oh, Chao Li, Wei Li, Lathika Mohanraj, Qing Cai, Mitchell S. Anscher, Youngman Oh |
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| description | <jats:p>Radiotherapy-induced fibrosis (RTIF) presents a challenge in radiotherapy for cancer patients. Although numerous studies have attempted to elucidate the mechanisms leading to RTIF, the pathogenesis of RTIF at the cellular and molecular level is still incompletely described. One key component involved in the post-radiation injury is the pleuripotent cytokine transforming growth factor (TGF)-β. TGF-β signaling pathway has been under intensive investigation about its critical role in radiation-induced fibroproliferative disease. Connective tissue growth factor (CTGF), also known as insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) is a potent regulator of fibroblast proliferation, cell adhesion, and stimulation of extracellular matrix production. CTGF is known as a major downstream mediator of the chronic fibrotic effects of TGF-β. Here we have demonstrated that irradiation and TGF-β induced CTGF, subsequently upregulates fibrotic factors such as fibronectin and type IV collagen. Furthermore, as HMG-CoA reductase inhibitors, statins inhibit expressions of CTGF and downstream fibrotic proteins in both normal human fetal fibroblasts (HFL-1) and human dermal fibroblasts (HDF) on TGF-β treatment or irradiation. Our study also demonstrates that simvastatin not only suppressed TGF-β-induced fibrosis through inhibition of CTGF production but also CTGF-induced fibrosis. We further show that simvastatin may act in a TGF-β-independent manner by inhibiting Rho kinase pathway. Taken together, these data suggest that radiotherapy may upregulate CTGF expression in a TGF-β-dependent and -independent manner, thereby enhancing expression of profibrotic factors and inducing lung fibrosis.</jats:p> |
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| spelling | Chao Li Wei Li Lathika Mohanraj Qing Cai Mitchell S. Anscher Youngman Oh 1929-2279 Neoplasia Research http://dx.doi.org/10.6000/1929-2279.2014.03.01.8 <jats:p>Radiotherapy-induced fibrosis (RTIF) presents a challenge in radiotherapy for cancer patients. Although numerous studies have attempted to elucidate the mechanisms leading to RTIF, the pathogenesis of RTIF at the cellular and molecular level is still incompletely described. One key component involved in the post-radiation injury is the pleuripotent cytokine transforming growth factor (TGF)-β. TGF-β signaling pathway has been under intensive investigation about its critical role in radiation-induced fibroproliferative disease. Connective tissue growth factor (CTGF), also known as insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) is a potent regulator of fibroblast proliferation, cell adhesion, and stimulation of extracellular matrix production. CTGF is known as a major downstream mediator of the chronic fibrotic effects of TGF-β. Here we have demonstrated that irradiation and TGF-β induced CTGF, subsequently upregulates fibrotic factors such as fibronectin and type IV collagen. Furthermore, as HMG-CoA reductase inhibitors, statins inhibit expressions of CTGF and downstream fibrotic proteins in both normal human fetal fibroblasts (HFL-1) and human dermal fibroblasts (HDF) on TGF-β treatment or irradiation. Our study also demonstrates that simvastatin not only suppressed TGF-β-induced fibrosis through inhibition of CTGF production but also CTGF-induced fibrosis. We further show that simvastatin may act in a TGF-β-independent manner by inhibiting Rho kinase pathway. Taken together, these data suggest that radiotherapy may upregulate CTGF expression in a TGF-β-dependent and -independent manner, thereby enhancing expression of profibrotic factors and inducing lung fibrosis.</jats:p> Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis Journal of Cancer Research Updates |
| spellingShingle | Chao Li, Wei Li, Lathika Mohanraj, Qing Cai, Mitchell S. Anscher, Youngman Oh, Journal of Cancer Research Updates, Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_full | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_fullStr | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_full_unstemmed | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_short | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| title_sort | multiple mechanisms for anti-fibrotic functions of statins on radiotherapy induced fibrosis |
| title_unstemmed | Multiple Mechanisms for Anti-Fibrotic Functions of Statins on Radiotherapy Induced Fibrosis |
| url | http://dx.doi.org/10.6000/1929-2279.2014.03.01.8 |