Investigation of cardiovascular regulation and multiple function of gastrointestinal peptides

• Project/Area Number: 16H05306
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MIYAZATO Mikiya 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (50291183)
• Co-Investigator(Kenkyū-buntansha): 日野 純 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40260351)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: ペプチド / ニューロメジン / 自律神経 / 循環調節 / グレリン

Outline of Final Research Achievements

To clarify the cardiovascular regulation and multiple functions of gastrointestinal peptides, 1) we searched for the endogenous ligands of the orphan receptors expressed in the vagal nerve ganglion, 2) we identified a novel peptide, neuromadin U precursor-related peptide (NURP), from rat brain and small intestine, and analyzed its function, and 3) we generated endothelial cell-specific C-type natriuretic peptide (CNP) transgenic mice and analyzed their effect in high fat diet-induced obesity.

Academic Significance and Societal Importance of the Research Achievements

研究代表者の研究室では、生体内に存在する新たな生理活性ペプチドを同定し、その機能を解明することにより、未知の生体機能調節機構を明らかにすることをテーマとして研究を進めてきた。今回、NURPと命名した新規ペプチドの発見に成功し、生体内の新たな調節機構を提示することができた。また、既知ペプチドであるCNPによる肥満およびその関連疾患に対する治療標的としての可能性が示唆された。

Research Products

• [Journal Article] Ghrelin and the heart (2019)
  • Author(s): Tokudome T, Otani K, Miyazato M, Kangawa K
  • Journal Title: Peptides Volume: 111 Pages: 42-46
  • DOI: 10.1016/j.peptides.2018.05.006
  • Peer Reviewed / Open Access
• [Journal Article] C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis (2018)
  • Author(s): Bae Cho-Rong、Hino Jun、Hosoda Hiroshi、Miyazato Mikiya、Kangawa Kenji
  • Journal Title: Life Sciences Volume: 209 Pages: 349-356
  • DOI: 10.1016/j.lfs.2018.08.031
  • Peer Reviewed / Open Access
• [Journal Article] Bone Morphogenetic Protein (BMP)-3b Gene Depletion Causes High Mortality in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy (2018)
  • Author(s): Ogawa Yuko、Tsuji Masahiro、Tanaka Emi、Miyazato Mikiya、Hino Jun
  • Journal Title: Frontiers in Neurology Volume: 9 Pages: 397-397
  • DOI: 10.3389/fneur.2018.00397
  • Peer Reviewed / Open Access
• [Journal Article] Adipocyte-specific expression of C-type natriuretic peptide suppresses lipid metabolism and adipocyte hypertrophy in adipose tissues in mice fed high-fat diet. (2018)
  • Author(s): Bae CR, Hino J, Hosoda H, Son C, Makino H, Tokudome T, Tomita T, Hosoda K, Miyazato M, Kangawa K.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 2093-2093
  • DOI: 10.1038/s41598-018-20469-z
  • Peer Reviewed / Open Access
• [Journal Article] Discovery of a human neuromedin U receptor 1-selective hexapeptide agonist with enhanced serum stability (2017)
  • Author(s): Takayama T, Mori K, Tanaka A, Nomura E, Sohma Y, Mori M, Taguchi A, Taniguchi A, Sakane T, Yamamoto A,& Minamino N, Miyazato M, Kangawa K, Hayashi Y
  • Journal Title: J Med Chem Volume: 60 Pages: 5228-5234
  • Peer Reviewed
• [Journal Article] Identification of neuromedin U precursor-related peptide and its possible role in the regulation of prolactin release (2017)
  • Author(s): Mori Kenji、Ida Takanori、Fudetani Mami、Mori Miwa、Kaiya Hiroyuki、Hino Jun、Nakahara Keiko、Murakami Noboru、Miyazato Mikiya、Kangawa Kenji
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-017-10319-9
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of C-type Natriuretic Peptide in Endothelial Cells Protects against Insulin Resistance and Inflammation during Diet-induced Obesity. (2017)
  • Author(s): Bae CR, Hino J, Hosoda H, Arai Y, Son C, Makino H, Tokudome T, Tomita T, Kimura T, Nojiri T, Hosoda K, Miyazato M, Kangawa K.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 9807-9807
  • DOI: 10.1038/s41598-017-10240-1
  • Peer Reviewed / Open Access
• [Journal Article] Neuromedin U precursor-related peptide (NURP) exerts neuromedin U-like sympathetic nerve action in the rat (2017)
  • Author(s): Ensho Takuya、Maruyama Keisuke、Mori Kenji、Miyazato Mikiya、Kangawa Kenji、Nakahara Keiko、Murakami Noboru
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 492 Issue: 3 Pages: 412-418
  • DOI: 10.1016/j.bbrc.2017.08.084
  • Peer Reviewed
• [Journal Article] Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity. (2017)
  • Author(s): Hino J, Nakatani M, Arai Y, Tsuchida K, Shirai M, Miyazato M, Kangawa K
  • Journal Title: Int J Obes Volume: 41 Issue: 4 Pages: 483-488
  • DOI: 10.1038/ijo.2017.15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice. (2017)
  • Author(s): Zenitani M, Nojiri T, Kimura T, Hosoda H, Miura K, Hino J, Nakahata K, Uehara S, Miyazato M, Oue T, Okuyama H, Kangawa K
  • Journal Title: Cancer Chemother Pharmacol Volume: 79 Issue: 2 Pages: 363-368
  • DOI: 10.1007/s00280-016-3221-5
  • Peer Reviewed / Open Access
• [Journal Article] Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice : ANP for pulmonary fibrosis. (2017)
  • Author(s): Okamoto A, Nojiri T, Konishi K, Tokudome T, Miura K, Hosoda H, Hino J, Miyazato M, Kyomoto Y, Asai K, Hirata K, Kangawa K
  • Journal Title: Respir Res Volume: 18 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s12931-016-0492-7
  • Peer Reviewed / Open Access
• [Journal Article] Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice. (2016)
  • Author(s): Nojiri T, Hosoda H, Kimura T, Tokudome T, Miura K, Takabatake H, Miyazato M, Okumura M, Kangawa K
  • Journal Title: Peptides Volume: 82 Pages: 85-91
  • DOI: 10.1016/j.peptides.2016.06.003
  • Peer Reviewed
• [Journal Article] Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia. (2016)
  • Author(s): Nojiri T, Hosoda H, Zenitani M, Tokudome T, Kimura T, Miura K, Miyazato M, Okumura M, Kangawa K
  • Journal Title: Cancer Chemother Pharmacol Volume: 78 Issue: 1 Pages: 191-197
  • DOI: 10.1007/s00280-016-3075-x
  • Peer Reviewed / Open Access