Basic research on the control treatment of pulmonary fibrosis by adenoviral vector which promotes selective gene expression
| Project/Area Number |
15591485
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
INOUE Kiyotoshi Graduate school medicine research course, Graduate school medicine research course, Lecturer, 大学院・医学研究科, 講師 (50193579)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IKEDA Kazuo Osaka City University, Graduate school medicine research course, assistant professor, 大学院・医学研究科, 助教授 (80275247)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Keywords | pulmonary fibrosis / Cre / loxP system / adenovirus vector / fibroblast / alveolar epithelial cell / BMP7 / Id2 / Id3 / ld2 / ld3 / TK / Akt / YB-1 |
|---|
| Research Abstract |
Mesenchymal cells such as fibroblasts and myofibroblasts are the principle matrix-producing cells during pulmonary fibrogenesis. TGF β signaling plays an important role in stimulating the expression of type I collagen, the major component of extracellular matrix. Recently, a member of TGFβ superfamily, bone morphogenetic protein (BMP)-7, was reported to oppose TGFβ1 in fibrogenesis. Here, we have addressed the effects of gene transfer of BMP-7 on fibrogenic reaction using pulmonary myofibroblastic cell lines, in which collagen promoter activity was detected by luciferase assay. To do so, we first established cell lines from lung tissues of transgenic mice harboring the collagen 1A2 upstream sequence. These cell lines showed spindle shape, and expressed vimentin and aSMA, but not E-cadherin, which demonstrates that they are derived from lung myofibroblasts. They showed luciferase activity that was dose-dependent on TGFβ1 stimulation. This activity was also up-regulated by overexpression of Smad3 and down-regulated by that of Smad7. These cell lines were used to evaluate the effect of BMP-7 for following examination. In immunocytochemical examination, ectopic expression of BMP-7 (Ad-BMP-7) led to nuclear localization of phospho-Smadl/5/8 and suppressed that of Smad3. Ad-BMP-7 decreased collagen 1A2 promoter-dependent luciferase activity. Real-time RT PCR showed that Ad-BMP-7 suppressed the expression of collagen 1A2, tissue inhibitor of metalloproteinase and increased that of inhibitor of differentiation (Id) 2 and 3, which opposes TGFβ signaling. Furthermore, ectopic expression of Id2 and ID decreased collagen 1A2 promoter-dependent luciferase activity in pulmonary myofibroblasts. In conclusion, these data demonstrate that BMP-7 antagonizes TGFβ-dependent fibrogenesis by expression of 1d2 in mouse pulmonary myofibroblast cell lines.
|
Report
(3 results)
Research Products
(38 results)
-
-
-
-
-
[Journal Article] Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial-mesenchymal transition of lens epithelium in mice.2004
Author(s)
Saika S, Ikeda K, Yamanaka O, Sato M, Muragaki Y, Ohnishi Y, Ooshima A, Nakajima Y, Namikawa K, Kiyama H, Flanders KC, Roberts AB.
-
Journal Title
Lab Invest 84
Pages: 1259-1270
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.1997
Author(s)
Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P.
-
Journal Title
Embo J 16
Pages: 5353-5362
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
