Role of molecular clock on the homeostatic communication between each organ in chronic kidney disease

• Project/Area Number: 25253038
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyushu University
• Principal Investigator: Ohdo Shigehiro 九州大学, 薬学研究科(研究院), 教授 (00223884)
• Co-Investigator(Kenkyū-buntansha): Koyanagi Satoru 九州大学, 薬学研究科(研究院), 准教授 (60330932) ; Matsunaga Naoya 九州大学, 大学院薬学研究院, 准教授 (10432915)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000); Fiscal Year 2015: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2014: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000); Fiscal Year 2013: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
• Keywords: 薬学 / 腎障害 / 恒常性 / 幹細胞 / 分子時計

Outline of Final Research Achievements

Chronic kidney disease (CKD) increases the disease risk of liver as well as that of kidney. However, the mechanisms remain unclear. In the present study, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6 nephrectomy (5/6Nx) mice led to the decreased expression of the Dbp gene, controlling the function of cytochrome P450 (CYPs). Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, decreased in 5/6Nx mice. The accumulation of serum retinol induced renal apoptosis in 5/6Nx mice. The alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were decreased by an anti-TGF-β1 antibody.The present study suggests that the chronic renal failure in 5/6Nx mice causes the inflammation by the abnormal signal transduction in high TGF-βexpression from the kidney and decrease the function of CYPs in liver. Finally, the cell cycle regulatory factor in kidney plays an important role of CKD and may be a promising therapeutic target in the treatment of CKD.

Research Products

• [Journal Article] Different roles of negative and positive components of the circadian clock in oncogene-induced neoplastic transformation. (2016)
  • Author(s): Katamune C, Koyanagi S, Shiromizu S, Matsunaga N, Shimba S, Shibata S, Ohdo S.
  • Journal Title: J Biol Chem. Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression. (2016)
  • Author(s): Okazaki F, Matsunaga N, Okazaki H, Azuma H, Hamamura K, Tsuruta A, Tsurudome Y, Ogino T, Hara Y, Suzuki T, Hyodo K, Ishihara H, Kikuchi H, To H, Aramaki H, Koyanagi S, Ohdo S
  • Journal Title: The Journal of biological chemistry Volume: 291 Issue: 13 Pages: 7017-7028
  • DOI: 10.1074/jbc.m115.713412
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction. (2016)
  • Author(s): Hamamura K, Matsunaga N, Ikeda E, Kondo H, Ikeyama H, Tokushige K, Itcho K, Furuichi Y, Yoshida Y, Matsuda M, Yasuda K, Doi A, Yokota Y, Amamoto T, Aramaki H, Irino Y, Koyanagi S, Ohdo S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 10 Pages: 4913-4927
  • DOI: 10.1074/jbc.m115.696930
  • Peer Reviewed
• [Journal Article] Modulation of peroxisome proliferator-activated receptor-α activity by bile acids causes circadian changes in the intestinal expression of Octn1/Slc22a4 in mice. (2015)
  • Author(s): Wada E, Koyanagi S, Kusunose N, Akamine T, Masui H, Hashimoto H, Matsunaga N, Ohdo S.
  • Journal Title: Mol Pharmacol Volume: 87 Issue: 2 Pages: 314-322
  • DOI: 10.1124/mol.114.094979
  • Peer Reviewed / Open Access
• [Journal Article] Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1. (2014)
  • Author(s): Okamura A, Koyanagi S, Dilxiat A, Kusunose N, Chen JJ, Matsunaga N, Shibata S, Ohdo S.
  • Journal Title: J Biol Chem. Volume: 289(36) Issue: 36 Pages: 25296-25305
  • DOI: 10.1074/jbc.m114.577023
  • Peer Reviewed / Open Access
• [Journal Article] 24-Hour Rhythm of Aquaporin-3 Function in the Epidermis Is RegUlated by Molecular Clocks (2014)
  • Author(s): Naoya Matsunaga, Kazufumi Itcho, Kengo Hamamura, Eriko Ikeda, Hisako Ikeyama, Yoko Furuichi, Miyako Watanabe, Satoru Koyanagi, Shigehiro Ohdo
  • Journal Title: Joumal of lnvestigative Dermatology Volume: (印刷中) Issue: 6 Pages: 1636-1644
  • DOI: 10.1038/jid.2014.13
  • Peer Reviewed
• [Journal Article] Renal circadian clock regulates the dosing-time dependency of cisplatin-induced nephrotoxicity in mice. (2014)
  • Author(s): Oda M, Koyanagi S, Tsurudome Y, Kanemitsu T, Matsunaga N, Ohdo S.
  • Journal Title: Mol Pharmacol Volume: 85 Issue: 5 Pages: 715-722
  • DOI: 10.1124/mol.113.089805
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma (2014)
  • Author(s): Okazaki, H., Matsunaga, N., Fujioka, T., Okazaki, F., Akagawa, Y., Tsurudome, Y., Ono, M,. Kuwano, M., Koyanagi, S., and Ohdo, S.
  • Journal Title: Cancer Res. Volume: 74 Issue: 2 Pages: 543-551
  • DOI: 10.1158/0008-5472.can-12-3241
  • Peer Reviewed
• [Presentation] がん細胞の薬剤感受性の概日リズム制御メカニズムと投薬のタイミング. (2013)
  • Author(s): 大戸茂弘、小柳悟、松永直哉
  • Organizer: 第86回 日本生化学会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Chronopharmacological aspects of transporters (2013)
  • Author(s): 大戸茂弘、小柳悟、松永直哉
  • Organizer: 日本薬物動態学会 第28回年会
  • Place of Presentation: 東京
  • Invited