| Project/Area Number |
14571024
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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 |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
MORIYAMA Toshiki Osaka Univ., School of Health and Sport Sciences, Assistant Professor, 健康体育部, 助教授 (30283815)
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| Co-Investigator(Kenkyū-buntansha) |
MIWA Takashi Osaka Univ., Genome Information Research Center, 遺伝情報実験施設, 助教授 (20174229)
IMI Enyu Osaka Univ., Graduate School of Medicine, 大学院・医学系研究科, 講師 (00223305)
安東 明夫 大阪大学, 健康体育部, 教授 (00028656)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | smooth muscle a-action / C / EBPδ / all trans retinoic acid / myofibroblast / kockaut mouse / C / 平滑筋アルファアクチン / CEBPα / CArG element |
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| Research Abstract |
Myofibroblast is regarded to play pivotal roles in pathological process of a wide variety of organs such as lung, liver and kidney, by producing several inflammatory cytokines and extracellular matrices. However, the mechanisms by which transdifferentiation from original cell to myofibroblast occurs are still unclear. The expression of smooth muscle a-actin is the most characteristic feature of myofibroblast, and we speculated any factors that promote smooth muscle a-actin expression might be the key of transdifferenfiation to myofibroblast and disease exacerbation. A transcription factor C/EBPd was identified to bind to the sequence including CArG motif of smooth muscle a-actin intron 1 and to increase transcriptional activity of this promoter. The expression of smooth muscle a-actin and C/EBPd was evidently up-regulated in rat anti-Thy1 glomerulonephritis and mouse Habu-venom glomerulonephritis, which are models of mesangioproliferative glomerulonephritis. In the latter model, C/EBPd knockout mice demonstrated, in comparison to wild-type mice, significantly less smooth muscle a-actin expression in the glomerular area on day 8, which was decreased similarly on day 14, and less renal functional deteriolation. These data suggest the important role of C/EBPd in myofibroblast transdifferentiation and glonerulonephritis exacerbation.
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