| RRC ID |
10930
|
| 著者 |
Ono Y, Sensui H, Okutsu S, Nagatomi R.
|
| タイトル |
Notch2 negatively regulates myofibroblastic differentiation of myoblasts.
|
| ジャーナル |
J Cell Physiol
|
| Abstract |
Myofibroblasts are one of the key cellular components involved in fibrosis of skeletal muscle as well as in other tissues. Transforming growth factor-beta1 (TGF-beta1) stimulates differentiation of mesenchymal cells into myofibroblasts, but little is known about the regulatory mechanisms of myofibroblastic differentiation. Since Notch2 was shown to be downregulated in TGF-beta1-induced non-muscle fibrogenic tissue, we investigated whether Notch2 also has a distinctive role in myofibroblastic differentiation of myogenic cells induced by TGF-beta1. TGF-beta1 treatment of C2C12 myoblasts led to expression of myofibroblastic marker alpha-smooth muscle actin (alpha-SMA) and collagen I with concomitant downregulation of Notch2 expression. Overexpression of active Notch2 inhibited TGF-beta1-induced expression of alpha-SMA and collagen I. Interestingly, transient knockdown of Notch2 by siRNA in C2C12 myoblasts and primary cultured muscle-derived progenitor cells resulted in differentiation into myofibroblastic cells expressing alpha-SMA and collagen I without TGF-beta1 treatment. Furthermore, we found Notch3 was counter-regulated by Notch2 in C2C12 cells. These findings suggest that Notch2 is inhibiting differentiation of myoblasts into myofibroblasts with downregulation of Notch3 expression.
|
| 巻・号 |
210(2)
|
| ページ |
358-69
|
| 公開日 |
2007-2-1
|
| DOI |
10.1002/jcp.20838
|
| PMID |
17044085
|
| MeSH |
Actins / drug effects
Actins / metabolism
Animals
Cell Differentiation / drug effects
Cell Differentiation / genetics*
Cell Line
Collagen Type I / drug effects
Collagen Type I / metabolism
Down-Regulation / drug effects
Down-Regulation / genetics*
Fibroblasts / cytology
Fibroblasts / metabolism*
Fibrosis / genetics
Fibrosis / metabolism
Fibrosis / physiopathology
Gene Expression Regulation, Developmental / drug effects
Gene Expression Regulation, Developmental / genetics
Male
Mice
Mice, Inbred C57BL
Muscular Diseases / genetics
Muscular Diseases / metabolism
Muscular Diseases / physiopathology
Myoblasts, Skeletal / cytology
Myoblasts, Skeletal / drug effects
Myoblasts, Skeletal / metabolism*
RNA Interference
RNA, Small Interfering
Receptor, Notch2 / metabolism*
Receptor, Notch3
Receptors, Notch / metabolism
Regeneration / drug effects
Regeneration / genetics
Transforming Growth Factor beta1 / metabolism
Transforming Growth Factor beta1 / pharmacology
Wound Healing / drug effects
Wound Healing / genetics
|
| IF |
5.546
|
| 引用数 |
48
|
|
WOS 分野
|
PHYSIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
