| Project/Area Number |
22590351
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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 |
Experimental pathology
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| Research Institution | Fujita Health University |
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Principal Investigator |
SHIZUKO Nagao 藤田保健衛生大学, 疾患モデル教育研究センター, 准教授 (20183527)
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| Co-Investigator(Kenkyū-buntansha) |
MASANORI Kugita 藤田保健衛生大学, 疾患モデル教育研究センター, 助教 (50440681)
YOSHIHARA Daisuke 藤田保健衛生大学, 疾患モデル教育研究センター, 助教 (70454402)
MORITA Miwa 藤田保健衛生大学, 疾患モデル教育研究センター, 助教 (90329699)
YAGYU Shigeru 藤田保健衛生大学, 疾患モデル教育研究センター, 助教 (10200479)
YAMAGUCHI Tamio 藤田保健衛生大学, 疾患モデル教育研究センター, 研究生 (70536292)
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| Co-Investigator(Renkei-kenkyūsha) |
HIKI Yoshiyuki 藤田保健衛生大学, 医療科学部, 教授 (20156566)
KURAHASHI Hiroki 藤田保健衛生大学, 医療科学部, 教授 (30243215)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 多発性嚢胞腎 / PPAR / ERK / mTOR / TGF / SCD1 / 細胞増殖 / 線維 / 核内受容体 / 線維化 / 嚢胞 / 細胞内情報伝達 / polycystic kidney / polycystic liver / S6 |
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| Research Abstract |
Polycystic kidney disease (PKD) produces aberrant cell proliferation, interstitial fibrosis, and fluid accumulation in the kidneys and liver. PKD is characterized by increased activity in the cAMP/PKA/B-RAF/MEK/ER (ERK), Ca2+/PI3K/AKT/mTOR/S6K/S6 (mTOR), and TGFβ signaling pathways. Peroxisome proliferator-activated receptor (PPAR)γ, a member of the ligand-dependent nuclear receptor superfamily, plays important roles in cell proliferation, fibrosis, and inflammation in the kidneys and liver. In the present study, we evaluated treatment with pioglitazone (PIO), a PPARγ agonist, in a disease model rat of PKD. PIO decreased progression of polycystic kidney and liver disease with reduction of ERK, mTOR and TGFβ activities, and downregulated cell cycle and cell proliferation related to the EGF, PDGF, and JNK pathways in this model. A key enzyme for the effect of PIO was stearoyl-coenzyme A desaturase 1 (SCD1). These findings suggest that PPARγ agonists may represent a novel therapeut c approach for the treatment of renal and hepatic manifestations of PKD.
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