| Project/Area Number |
10470217
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
IMAI Enyu Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00223305)
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| Co-Investigator(Kenkyū-buntansha) |
ISAKA Yoshitaka Osaka University Graduate School of Medicine, Medical Staff, 医学部・附属病院, 医員
KANEDA Yasuhumi Osaka University Graduate School of Medicine, Professer, 医学系研究科, 教授 (10177537)
MORIYAMA Toshiki Osaka University Graduate School of Medicine, Lecturer, 健康体育部, 講師 (30283815)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | TGF-β / antisense / gene therapy / HVJ-liposome / interstitial fibrosis / HVJリポソーム法 / 糖尿病性腎症 / 糸球体肥大 / 糸球体基底膜肥厚 / 進行性腎障害 |
|---|
| Research Abstract |
There is little doubt that molecular biological intervention therapy has come of age and tremendous excitements have emerged from its potential. A gene transfer technique, HVJ-liposome method is now applicable to the analysis of molecular aspects in pathophysiology of renal diseases, and further to a tool for gene therapy. We demonstrated that continuous delivery of chimeric soluble TGF-β receptor from the gene transferred skeletal muscle also inhibits the extracellular matrix expansion in experimental glomerulonephritis. Furthermore, we challenged whether in vivo gene transfer of antisense ODNs for TGF-β into interstitial fibroblasts can suppress the progression of interstitial fibrosis in unilateral ureteral obstruction model rats. Introduction of TGF-β1 antisense ODNs significantly reduced levels of TGF-β1 and types I collagen mRNA expression in obstructed kidneys, and consequently prevented the extent of interstitial fibrosis following ureteral obstruction. Taken together with clinical observation that up-regulation of TGF-β plays an important role in the formation of various kidney fibrosis, the manipulation of the overexpression of TGF-β may provide a novel way of therapeutic intervention to ameliorate the progression of the renal diseases.
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