Roles of Pin1 and PAR 14 on the metabolic regulations
Project/Area Number |
26293219
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Hiroshima University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
中津 祐介 広島大学, 医歯薬保健学研究院(医), 助教 (20452584)
福嶋 俊明 広島大学, 医歯薬保健学研究院, 助教 (70543552)
|
Co-Investigator(Renkei-kenkyūsha) |
SAKODA HIDEYUKI 東京大学, 附属病院, 助教 (50376464)
FUJISHIRO MIDORI 東京大学, 附属病院, 助教 (50420211)
HONDA HIROAKI 広島大学, 原爆放射線医科学研究所, 教授 (40245064)
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Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
|
Keywords | 代謝 / 糖尿病 / Pin1 / インスリン / プロリン異性化酵素 / メタボリックシンドローム / 肥満 / シグナル伝達 / 肝細胞 / LUBAC / TFG / メタボシックシンドローム / インスリン抵抗性 / インスリン分泌 |
Outline of Final Research Achievements |
Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. We have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis (NASH) and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-kappaB p65.
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] USP15 attenuates IGF-I signaling by antagonizing Nedd4-induced IRS-2 ubiquitination2017
Author(s)
Fukushima, T., Yoshihara, H., Furuta, H., Hakuno, F., Saeki, Y., Iemura, SI., Natsume, T., Nakatsu, Y., Kamata, H., Asano, T., Komada, M., Takahashi, SI.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 484
Pages: 522-528
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduced SHARPIN and LUBAC Formation May Contribute to CCl4- or Acetaminophen-Induced Liver Cirrhosis in Mice.2017
Author(s)
Yamamotoya, T., Nakatsu, Y., Matsunaga, Y., Fukushima, T., Yamazaki, H., Kaneko, S., Fujishiro, M., Kikuchi, T., Kushiyama, A., Tokunaga, F., Asano, T., Sakoda, H.
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Journal Title
Int. J. Mol. Sci.
Volume: 18
Pages: 326-326
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of uric acid metabolism-related inflammation in the pathogenesis of metabolic syndrome components such as atherosclerosis and non-alcoholic steatohepatitis2016
Author(s)
Kushiyama, A., Nakatasu, Y., Matsunaga, Y., Yamamotoya, T., Mori, K., Ueda, K., Sakoda, H., Fujishiro, M., Ono, H., and Asano, T.
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Journal Title
Mediators Inflamm.
Volume: 2016
Pages: 8603164-8603164
Related Report
Peer Reviewed / Open Access
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[Journal Article] Involvement of Resistin-like molecule beta in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice2016
Author(s)
Okubo H., Kushiyama, A., Sakoda, H., Nakatsu, Y., Iizuka, M., Taki, N., Fujishiro, M., Fukushima, T., Kamata, H., Nagamachi, A., Inaba, T., Nishimura, F., Katagiri, H., Asahara, T., Yoshida, Y., Chonan, O., Encinas, J., and Asano, T.
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Journal Title
Scientific Reports
Volume: 6
Pages: 20157-20157
Related Report
Peer Reviewed / Open Access
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[Journal Article] Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.2016
Author(s)
Nakatsu, Y., Matsunaga, Y., Yamamotoya, T., Ueda, K., Inoue, Y., Mori, K., Sakoda, H., Fujishiro, M., Ono, H., Kushiyama, A., and Asano, T.
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Journal Title
Int. J. Mol. Sci.
Volume: 17
Related Report
Peer Reviewed / Open Access
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[Journal Article] IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes.2016
Author(s)
Shinjo, T., Iwashita, M., Yamashita, A., Sano, T., Tsuruta, M., Matsunaga, H., Sanui, T., Asano, T., and Nishimura, F.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 477
Pages: 241-6
Related Report
Peer Reviewed / Open Access
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[Journal Article] Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus.2015
Author(s)
Qiang, S., Nakatsu, Y., Seno, Y., Fujishiro, M., Sakoda, H., Kushiyama, A., Mori, K., Matsunaga, Y., Yamamotoya, T., Kamata, H., and Asano, T.
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Journal Title
Diabetol. Metab. Syndr.
Volume: 7
Pages: 104-104
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Prolyl Isomerase Pin1 Negatively Regulates AMPK by Associating with the CBS Domain in the γ-subunit.2015
Author(s)
Nakatsu, Y., Iwashita, M., Sakoda, H., Ono, H., Nagata, K., Matsunaga, Y., Fukushima, T., Fujishiro, M., Kushiyama, A., Kamata, H., Takahashi, S., Katagiri, H., Honda, H., Kiyonari, H., Uchida, T., and Asano, T.
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Journal Title
J. Biol. Chem.
Volume: 290
Pages: 24255-24266
Related Report
Peer Reviewed / Open Access
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[Journal Article] A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.2015
Author(s)
Uno, K., Yamada, T., Ishigaki, Y., Imai, J., Hasegawa, Y., Sawada, S., Kaneko, K., Ono, H., Asano, T., Oka, Y., and Katagiri, H.
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Journal Title
Nat. Commun.
Volume: 6
Pages: 7940-7940
Related Report
Peer Reviewed / Open Access
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[Journal Article] Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet.2015
Author(s)
Shiwa, M., Yoneda, M., Okubo, H., Ohno, H., Kobuke, K., Monzen, Y., Kishimoto, R., Nakatasu, Y., Asano, T., and Kohno, N.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis.2015
Author(s)
Matsunaga, Y., Nakatsu, Y., Fukushima, T., Okubo, H., Iwashita, M., Sakoda, H., Fujishiro, M., Yamamotoya, T., Kushiyama, A., Takahashi, S., Tsuchiya, Y., Kamata, H., Tokunaga, F., Iwai, K., and Asano, T.
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Journal Title
Mediators Inflamm.
Volume: 12
Pages: 125380-125380
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-fat diet feeding significantly attenuates anagliptin-induced regeneration of islets of Langerhans in streptozotocin-induced diabetic mice.2015
Author(s)
Shinjo, T., Nakatsu, Y., Iwashita, M., Sano, T., Sakoda, H., Ishihara, H., Kushiyama, A., Fujishiro, M., Nishimura, F., and Asano, T.
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Journal Title
Diabetol. Metab. Syndr.
Volume: 7
Pages: 50-50
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling.2015
Author(s)
Sano, T., Iwashita, M., Nagayasu, S., Yamashita, A., Shinjo, T., Hashikata, A., Asano, T., Kushiyama, A., Ishimaru, N., Takahama, Y., and Nishimura, F.
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Journal Title
Obesity
Volume: 23
Pages: 1460-1471
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pin1 Inhibitor Juglone Exerts Anti-Oncogenic Effects on LNCaP and DU145 Cells despite the Patterns of Gene Regulation by Pin1 Differing between These Cell Lines.2015
Author(s)
Kanaoka, R., Kushiyama, A., Seno, Y., Nakatsu, Y., Matsunaga, Y., Fukushima, T., Tsuchiya, Y., Sakoda, H., Fujishiro, M., Yamamotoya, T., Kamata, H., Matsubara, A., and Asano, T.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation.2015
Author(s)
Shinjo, T., Nakatsu, Y., Iwashita, M., Sano, T., Sakoda, H., Ishihara, H., Kushiyama, A., Fujishiro, M., Fukushima, T., Tsuchiya, Y., Kamata, H., Nishimutra, F., and Asano, T.
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Journal Title
Am. J. Physiol. Endocrinol Metab.
Volume: 309
Related Report
Peer Reviewed / Open Access
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[Journal Article] The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model.2015
Author(s)
Nakatsu, Y., Seno, Y., Kushiyama, A., Sakoda, H., Fujishiro, M., Katasako, A., Mori, K., Matsunaga, Y., Fukushima, T., Kanaoka, R., Yamamotoya, T., Kamata, H., and Asano, T.
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Journal Title
Am. J. Physiol. Gastrointest Liver Physiol.
Volume: 309
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity2015
Author(s)
Fukushima, T., Yoshihara, H., furuta, H., Kamei, H., Hakuno, F., Luan, J., Duan, C., Saeki, Y., Tanaka, K., Iemura, S., Natsume, T., Chida, K., Nakatsu, Y., Kamata, H., Asano, T., and Takahashi, S.
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Journal Title
Nat. Commun.
Volume: 6
Pages: 6780-6780
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model.2015
Author(s)
Okubo, H., Nakatsu, Y., Sakoda, H., Kushiyama, A., Fujishiro, M., Fukushima, T., Matsunaga, Y., Ohno, H., Yoneda, M., Kamata, H., Shinjo, T., Iwashita, M., Nishimura, F., and Asano, T.
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Journal Title
Am. J. Physiol. Gastrointest Liver Physiol.
Volume: 308
Related Report
Peer Reviewed / Open Access
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[Journal Article] Insulin receptor substrate-4 binds to Slingshot-1 phosphatase and promotes cofilin dephosphorylation.2014
Author(s)
Homma, Y., Kanno, S., Sasaki, K., Nishita, M., Yasui, A., Asano, T., Ohashi, K., and Mizuno, K.
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Journal Title
J. Biol. Chem.
Volume: 289
Pages: 26302-13
Related Report
Peer Reviewed
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[Journal Article] A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation.2014
Author(s)
Mori, T., Hidaka, M., Ikuji, H., Yoshizawa, I., Toyohara, H., Okuda, T., Uvhida, C., Asano, T., Yotsu-Yamashita, M., and Uchida, T..
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Journal Title
Biosci. Biotechnol. Biochem.
Volume: 78
Pages: 832-8
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[Journal Article] Mediobasal hypothalamic PTEN modulates hepatic insulin resistance independently of food intake in rats.2014
Author(s)
Sumita, T., Ono, H., Suzuki, T., Inukai, K., Katagiri, H., Asano, T., Katayama, S., and Awata, T.
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Journal Title
Am. J. Physiol. Endocrinol Metab.
Volume: 307
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[Journal Article] Insulin receptor substrate-1 associates with small nucleolar RNA which contributes to ribosome biogenesis.2014
Author(s)
Ozoe, A., Sone, M., Fukushima, T., Kataoka, N., Chida, K., Asano, T., Hakuno, F., and Takahashi, S.
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Journal Title
Front Endocrinol.
Volume: 5
Pages: 1-12
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[Journal Article] The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease.2014
Author(s)
Hashikata, A., Yamashita, A., Suzuki, S., Nagayasu, S., Shinjo, T., Taniguchi, A., Fukushima, M., Nakai, Y., Nin, K., Watanabe, N., Asano, T., Abiko, Y., Kushiyama, A., Nagasaka, S.,and Nishimura, F.
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Journal Title
Nephrol. Dial. Transplant.
Volume: 29
Pages: 611-8
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