TGF-β1 induces fibroblast proliferation partly through activation of Raf/MEK/ERK signaling pathway by inhibition of Raf-kinase inhibitor protein expression
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- Kambe Yuki
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
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- Yamazaki Takehiko
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
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- Nakano Hajime
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
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- Hanada Katsumi
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
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- Tamai Katsuto
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
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- Tsuchida Shigeki
- Departments of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine
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- Sawamura Daisuke
- Departments of Dermatology, Hirosaki University Graduate School of Medicine
Bibliographic Information
- Other Title
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- TGF-β1 Induces Fibroblast Proliferation Partly Through Actibation of RaF/MEK/ERK Signaling Pathway by Inhibition of RAF-KINASE Inhibitor Protein Expression
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Description
The Raf-kinase inhibitor protein (RKIP) physically binds to Raf and MEK, and inhibits the Raf/MEK/ERK signaling pathway. Transforming growth factor (TGF)-β1 is a multifunctional cytokine that has a proliferative effect on fibroblasts. A considerable effort has been applied to studies of cell growth inhibition by TGF-β1, whereas far less attention has been given to the elucidation of the mechanism of TGF-β1-induced growth stimulation. In this study, we revealed that TGF-β1 significantly enhanced the proliferation of normal human dermal fibroblasts (NHDFs). In addition, we showed that TGF-β1 inhibited the expression of RKIP mRNA and protein. Moreover, a transfection experiment demonstrated that overexpression of RKIP significantly inhibited NHDF cell growth. These data point to a relationship between enhanced NHDF cell growth and reduction of RKIP expression by TGF-β1, suggesting that TGF-β1 may induce fibroblast proliferation partly through the inhibition of RKIP. Furthermore, we revealed that EGF and PDGF-BB, known activators of the Raf/MEK/ERK signal transduction pathway, failed to modulate RKIP expression. Finally, TGF-β1 induced a transient phosphorylation of ERK1/2. Although detailed mechanisms of NHDF proliferation via RKIP are yet unknown, it will be important to investigate the molecular status of RKIP in certain proliferative diseases, such as keloids, in which TGF-β1 has been reported to play a pathogenic role by inducing hyperproliferation of dermal fibroblasts.
Journal
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- Hirosaki Medical Journal
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Hirosaki Medical Journal 66 (2-4), 120-126, 2016
Hirosaki University Graduate School of Medicine,Hirosaki Medical Society
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Details 詳細情報について
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- CRID
- 1390006740592659840
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- NII Article ID
- 130008046375
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- NII Book ID
- AN00211444
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- ISSN
- 24344656
- 04391721
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- HANDLE
- 10129/5807
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- NDL BIB ID
- 027278126
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- NDL
- CiNii Articles
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- Abstract License Flag
- Disallowed