2012 Fiscal Year Final Research Report
A novel therapeutic approach for cystic disease:Inhibition of intracellular signal transduction pathways by a nuclear receptor cascade
| 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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| Keywords | 多発性嚢胞腎 / PPAR / ERK / mTOR / TGF / SCD1 / 細胞増殖 / 線維 |
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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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Research Products
(53 results)
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[Journal Article] Global Gene ExpressionProfiling in PPAR-γ Agonist-TreatedKidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease.2012
Author(s)
Yoshihara D, Kugita M, Yamaguchi T, Aukema HM, Kurahashi H, Morita M, Hiki Y, Calvet JP, Wallace DP, Toyohara T, Abe T, Nagao S.
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Journal Title
PPAR Res
Volume: 2012
Pages: 695898
DOI
Peer Reviewed
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[Journal Article] Structure and function of the pancreas in the polycystic kidney rat2012
Author(s)
Yi L, Naruse S, Furuya S, Yamamoto A, Nakakuki M, Nagao S, Yoshihara D, Ko SB, Wei M, Kondo T, Ishiguro H
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Journal Title
Pancreas.
Volume: Nov;41(8)
Pages: 1292-8
DOI
Peer Reviewed
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[Journal Article] Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter.2011
Author(s)
Sekiguchi S, Suzuki A, Asano S, Nishiwaki-Yasuda K, Shibata M, Nagao S, Yamamoto N, Matsuyama M, Sato Y, Yan K, Yaoita E, Itoh M.
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Journal Title
Am J Physiol RenalPhysiol
Volume: 300(4)
Pages: F848-56
DOI
Peer Reviewed
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[Journal Article] The Raf kinase inhibitor PLX5568 slows cyst proliferation in rat polycystic kidney disease but promotes renal and hepatic fibrosis.2011
Author(s)
Buchholz B, Klanke B, Schley G, Bollag G, Tsai J, Kroening S, Yoshihara D, Wallace DP, Kraenzlin B, Gretz N, Hirth P, Eckardt KU, Bernhardt WM.
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Journal Title
Nephrol Dial Transplant
Volume: 26(11)
Pages: 3458-65
DOI
Peer Reviewed
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[Journal Article] Global gene expression profiling in early-stage polycystic kidney disease in the Han : SPRD Cy rat identifies a role for RXR signaling.2011
Author(s)
Kugita M, Nishii K, Morita M, Yoshihara D, Kowa-Sugiyama H, Yamada K, Yamaguchi T, Wallace DP, Calvet JP, Kurahashi H, Nagao S.
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Journal Title
Am J Physiol Renal Physiol
Volume: 300(1)
Pages: F177-F188
DOI
Peer Reviewed
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[Journal Article] Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease.2011
Author(s)
Togawa H, Nakanishi K, Mukaiyama H, Hama T, Shima Y, Sako M, Miyajima M, Nozu K, Nishii K, Nagao S, Takahashi H, Iijima K, Yoshikawa N.
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Journal Title
Am J Physiol RenalPhysiol
Volume: 300(2)
Pages: 511-520
DOI
Peer Reviewed
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[Presentation] HikiExtracorporeal A β Removal System(EARS) for Alzheimer' s Disease therapy: Novel Devices with fragments of hollow fibers removed Aβ effectively both in vitro and invivo.2012
Author(s)
Nobuya Kitaguchi, Takehiro Gotoh, Kazunori Kawaguchi1, Hideo Hori, Atsushi Ohashi, Shigeru Nakai, Shizuko Nagao, Shinji Ito, Tatsuro Mutoh, Yukio Yuzawa, Yoshiyuki
Organizer
Alzheimer's Association International Conference 2012
Place of Presentation
Vancouver, British Columbia. Canada
Year and Date
20120714-19
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[Presentation] Global gene expression profiling in kidneys of PPAR-γ agonist-treated PCK rats, an orthologous model of human ARPKD.2011
Author(s)
Yoshihara D, Kugita M, Kurahashi H, Morita M, Hiki Y, Yamaguchi T, Aukema HM, Wallace DP, Calvet JP, Toyohara T, Abe T, Nagao S.
Organizer
American Society of Nephrology 44th Annual Meeting & Scientific Exposition 2011
Place of Presentation
Philadelphia, PA USA
Year and Date
20111108-20121113
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[Presentation] Acceleration of Smad3 phosphorylation at linker regions via c-Jun NH2-terminal kinase (JNK) in cyst-lining epithelial cells in cpk mouse, a model of ARPKD.2011
Author(s)
Mukaiyama H, Nakanishi K, Hama T, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
Organizer
American Society of Nephrology 44th Annual Meeting & Scientific Exposition 2011
Place of Presentation
Philadelphia, PA USA
Year and Date
20111108-20121113
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[Presentation] Metabolomic Profiling of the Autosomal Dominant Polycystic Kidney Disease Rat Model.2011
Author(s)
Takafumi Toyohara, Takehiro Suzuki,Yasutoshi Akiyama, Daisuke Yoshihara, Eikan Mishima, Yoichi Takeuchi, Sadayoshi Ito, Shizuko Nagao, Tomoyoshi Soga, Takaaki Abe
Organizer
American Society of Nephrology 44th Annual Meeting & Scientific Exposition 2011
Place of Presentation
Philadelphia, PA USA
Year and Date
20111108-20121113
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[Presentation] PPAR-γagonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease.2011
Author(s)
Daisuke Yoshihara, Hiroki Kurahashi, M iwa Morita, Masano r i K ugit a, Yoshiyuki Hiki, Harold M Aukema, Tamio Yamaguchi, James P Calvet, Darren PWallace, Shizuko Nagao.
Organizer
World Congress of Nephrology 2011
Place of Presentation
Vancouver, Canada
Year and Date
20110404-12
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[Presentation] Thiazolidinedione Ameliorates Autosomal Recessive Polycystic Kidney and Liver Disease in the PCK Rat, an Orthologous Model of Human ARPKD.2010
Author(s)
Yoshihara D, Kurahashi H, Morita M, Kugita M, Hiki Y, Aukema HM, Yamaguchi T, Calvet JP, Wallace DP, Nagao S.
Organizer
American Society of Nephrology 43rd Annual Meeting & Scientific Exposition.
Place of Presentation
Denver, CO USA
Year and Date
20101116-21
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