Identification of a novel adipocyte-derived factor that elevates blood pressure using VIKING method
| Project/Area Number |
19K22793
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
横山 敦 東北大学, 医学系研究科, 助教 (20572332)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | アルドステロン合成酵素 / 脂肪細胞 / メタボリック症候群 / 治療抵抗性高血圧 / 新規創薬 / イオン交換クロマトグラフィー / アルドステロン / 質量分析 / VIKING法 / 高血圧 / CYP11B2 / ゲノム編集 / 肥満 |
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| Outline of Research at the Start |
本研究課題では、新たに開発されたゲノム編集技術（VIKING法）と生化学的手法を組み合わせることで、極微量の脂肪細胞由来の未知昇圧因子を同定し、その解析を行うことで肥満高血圧発症の分子機序解明を目的としている。この研究は、肥満高血圧の治療法開発のための分子基盤となり新たな創薬標的の提案や新規診断法の開発に繋がるのみならず、これまで同定不可能だった微量の活性因子の同定に応用されることが考えられ既存の研究アプローチを大きく変革・転換させる潜在性を有する。
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| Outline of Final Research Achievements |
Hypertension is a frequently observed complication among obese patients with metabolic syndrome. In this study, we aim to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression and aldosterone secretion that may induce obesity-related hypertension. We first differentiated mouse fibroblast 3T3-L1 cells into adipocytes, and collected their supernatants. The supernatants were incubated with human adrenocortical carcinoma H295R cells, and their CYP11B2 mRNA expression was measured by quantitative PCR with reverse transcription. The supernatants were then purified by anion-exchange chromatography and were further fractionated by LC-MS/MS. We then identified several candidate proteins and are investigating their function by shRNA.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の遂行により、脂肪細胞由来の未知の液性昇圧因子の本態が初めて明らかとなるとともに新規創薬のターゲットが明確化されることから、本邦で2,700万人と推定されるメタボリック症候群・予備軍患者中に数多く存在する肥満高血圧患者の診断・治療に大きな福音をもたらす事が可能となる。特に、肥満高血圧患者において顕著な治療抵抗性高血圧に対しては、新規創薬・治療法の開発に向けて大きく貢献できると期待される。
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein2021
Author(s)
Saijoh S, Nakamura-Shima M, Shibuya-Takahashi R, Ito R, Sugawara A, Yamazaki T, Imai T, Asada Y, Matsuura K, Iwai W, Wakui Y, Abue M, Kawamura S, Katayose Y, Fujimori H, Mochizuki M, Yasuda J, Yamaguchi K, Sugamura K,Satoh K, Katori Y, Tamai K.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 537
Pages: 132-139
DOI
Related Report
Peer Reviewed
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[Journal Article] FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes2020
Author(s)
Kagawa Y, Umaru BA, Shima H, Ito R, Zama R, Islam A, Kanno S, Yasui A, Sato S, Jozaki K, Shil SK, Miyazaki H, Kobayashi S, Yamamoto Y, Kogo H, Shimamoto-Mitsuyama C, Sugawara A, Sugino N, Kanamori M, Tominaga T, Yoshikawa T, Fukunaga K, Igarashi K, Owada Y
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Journal Title
Molecular Neurobiology
Volume: 57
Issue: 12
Pages: 4891-4910
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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