| RRC ID |
1943
|
| 著者 |
Izumi N, Mizuguchi S, Inagaki Y, Saika S, Kawada N, Nakajima Y, Inoue K, Suehiro S, Friedman SL, Ikeda K.
|
| タイトル |
BMP-7 opposes TGF-beta1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2.
|
| ジャーナル |
Am J Physiol Lung Cell Mol Physiol
|
| Abstract |
Mesenchymal cells, primarily fibroblasts and myofibroblasts, are the principal matrix-producing cells during pulmonary fibrogenesis. Transforming growth factor (TGF)-beta signaling plays an important role in stimulating the expression of type I collagen of these cells. Bone morphogenetic protein (BMP)-7, a member of the TGF-beta superfamily, has been reported to oppose the fibrogenic activity of TGF-beta1. Here, we have addressed the effects of BMP-7 on the fibrogenic activity of pulmonary myofibroblasts. We first established cell lines from the lungs of transgenic mice harboring the COL1A2 upstream sequence fused to luciferase. They displayed a spindle shape and expressed vimentin and alpha-smooth muscle actin, but not E-cadherin. COL1A2 promoter activity was dose dependently induced by TGF-beta1, which was further augmented by adenoviral overexpression of Smad3, but was downregulated by Smad7. Under the identical condition, adenoviral overexpression of BMP-7 attenuated the TGF-beta1-dependent COL1A2 promoter activity. By immunocytochemistry, the ectopic expression of BMP-7 led to the nuclear localization of phospho-Smad1/5/8 and suppressed that of Smad3. BMP-7 suppressed the expression of mRNAs for COL1A2 and tissue inhibitor of metalloproteinase-2 while increasing those of inhibitors of differentiation (Id) 2 and 3. Ectopic expression of Id2 and Id3 was found to decrease the COL1A2 promoter activity. Finally, BMP-7 and Id2 decreased TGF-beta1-dependent collagen protein secretion. In conclusion, these data demonstrate that BMP-7 antagonizes the TGF-beta1-dependent fibrogenic activity of mouse pulmonary myofibroblastic cells by inducing Id2 and Id3.
|
| 巻・号 |
290(1)
|
| ページ |
L120-6
|
| 公開日 |
2006-1-1
|
| DOI |
10.1152/ajplung.00171.2005
|
| PII |
00171.2005
|
| PMID |
16126788
|
| MeSH |
Animals
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins / pharmacology
Bone Morphogenetic Proteins / physiology*
Cell Line
Cell Nucleus / metabolism
Collagen / biosynthesis*
Collagen / genetics
Collagen Type I
Fibroblasts / drug effects
Fibroblasts / metabolism*
Fibroblasts / physiology
Inhibitor of Differentiation Protein 2 / pharmacology
Inhibitor of Differentiation Protein 2 / physiology*
Lung / metabolism*
Mice
Mice, Transgenic
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism*
Myocytes, Smooth Muscle / physiology
Phenotype
Promoter Regions, Genetic / drug effects
RNA, Messenger / antagonists & inhibitors
RNA, Messenger / metabolism
Smad Proteins / metabolism
Tissue Distribution / drug effects
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta / physiology*
Transforming Growth Factor beta1
|
| IF |
4.418
|
| 引用数 |
82
|
|
WOS 分野
|
PHYSIOLOGY
RESPIRATORY SYSTEM
|
| リソース情報 |
| ヒト・動物細胞 |
NIH3T3-3-4 |
