Investigation of molecular mechanism in the development of pulmonary emphysema and susceptibility to cigarette smoke-induced lung injury using transgenic animal models
| Project/Area Number |
18590837
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
SUGA Tatsuo Gunma University, Faculty of Medicine, ASSISTANT PROFESSOR (50334115)
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| Co-Investigator(Kenkyū-buntansha) |
KURABAYASHI Masahiko GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR (00215047)
ISOBE Zen GUNMA UNIVERSITY, Faculty of Medicine, ASSISTANT (10384041)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Transgenic animal model / Pulmonary emphysema / Calcification / Cbfa-1 / Notch signaling / HERP / 肺気腫 / 喫煙感受性 / Notch シグナル / klotho遺伝子欠損マウス / 喫煙 |
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| Research Abstract |
Homozygous mutant klotho mice show vascular calcification as well as alveolar wall calcification. We analyzed expression of bone-associated proteins and osteogenic transcription factor Cbfa-1 in calcified lesions of aorta obtained from homozygous mutant klotho mice. Immunohistochemical staining disclosed proliferation of Cbfa-1 positive cells in tunica media. RT-PCR showed upregulation of the osteoblast-marker genes coding osteopontin, osteonectin as well as Cbfa-1. These results indicate that vascular calcification observed in homozygous mutant klotho mice is not to be passive process.
The klotho gene expression is essential to maintaining pulmonary integrity during postnatal life. We focused on the role of the Notch signaling pathway, which has the potential to induce cell differentiation and proliferation, in maturation of lung and in the development of lung injury. The expression of HERP-2, transcriptional targets of Notch-signaling, was up-regulated in capillary and alveolar epithelial cells at 1 week of age. In bleomycin-induced lung injury model, we found the expression of HERP-2 decreased from day 1 through day 14 after bleomycin administration. These findings suggest that Notch signaling is related to maintaining pulmonary integrity, especially through proliferation of capillary and alveolar epithelial cells.
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Report
(3 results)
Research Products
(3 results)
