significance of micro RNA as biomarker in primary aldosteronism

• Project/Area Number: 19K07885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yoshimoto Takanobu 東京医科歯科大学, 医学部, 非常勤講師 (80297457)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アルドステロン / 副腎腫瘍 / マイクロRNA / miRNA

Outline of Research at the Start

原発性アルドステロン症は高血圧症全体の10％を占める二次性高血圧症である。特にPA の半数を占めるアルドステロン産生副腎皮質腺腫（はより重症度が高く、手術による治癒も期待できる事より、その臨床的意義は重要である。本研究では手術で得られたAPA腫瘍検体や患者血中のマイクロRNAを網羅的に解析し、原発性アルドステロン症におけるmiRNA検査を通じた病態の解明および診断マーカーとしての臨床応用を目指す。

Outline of Final Research Achievements

The present study was undertaken to comprehensively explore micro(mi)RNAs which are specifically expressed in aldosterone-producing adenoma (APAs), an adrenocortical tumor which causes hypertension through aldosterone hypersecretion. We characterized several unique miRNAs in surgical specimen of APAs by the combination of NGS and qPCR. Among these, we found that miR299 is associated with the regulation of HPSE expression, an enzyme involved in the degradation of heparan sulfate proteoglycan. MicroRNAome stud would be one of the important research methods for elucidating the pathogenesis of APAs.

Academic Significance and Societal Importance of the Research Achievements

アルドステロン産生腺腫（APA）の発症機序はいまだ不明な点が多いが、今回のAPA腫瘍組織におけるmiRNAの網羅的発現解析により、複数のmiRNAが特徴的な発現を示している事が明らかとなった。加えていくつかのmiRNAはAPAの病因あるいは病態と関連する各種遺伝子発現と相関しており、特にmiR299については細胞間基質の発現制御を介して腫瘍発生に関与する可能性が新たに示された。miRNAome研究は、APAの病態発生で未解明であった領域のさならなる解明に重要な役割を担うと考えられる。

Research Products

• [Journal Article] Diverse pathological lesions of primary aldosteronism and their clinical significance (2021)
  • Author(s): Nishimoto Koshiro、JRAS Study Group、Umakoshi Hironobu、Seki Tsugio、Yasuda Masanori、Araki Ryuichiro、Otsuki Michio、Katabami Takuyuki、Shibata Hirotaka、Ogawa Yoshihiro、Wada Norio、Sone Masakatsu、Okamura Shintaro、Izawa Shoichiro、Miyauchi Shozo、Yoshimoto Takanobu、Tsuiki Mika、Naruse Mitsuhide
  • Journal Title: Hypertension Research Volume: 44 Issue: 5 Pages: 498-507
  • DOI: 10.1038/s41440-020-00579-w
  • Peer Reviewed / Open Access
• [Journal Article] Diabetes Mellitus Itself Increases Cardio-Cerebrovascular Risk and Renal Complications in Primary Aldosteronism (2020)
  • Author(s): Saiki A、Otsuki M、Tamada D、Kitamura T、Shimomura I、Kurihara I、Ichijo T、Takeda Y、Katabami T、Tsuiki M、Wada N、Yanase T、Ogawa Y、Kawashima J、Sone M、Inagaki N、Yoshimoto T、Okamoto R、Takahashi K、Kobayashi H、Tamura K、Kamemura K、Yamamoto K、Izawa S、Kakutani M、Yamada M、Tanabe A、Naruse M
  • Journal Title: The Journal of Clinical Endocrinology & Metabolism Volume: 105 Issue: 7 Pages: e2531-e2537
  • DOI: 10.1210/clinem/dgaa177
  • NAID: 120006953396
  • Peer Reviewed
• [Journal Article] Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism. (2020)
  • Author(s): Ohno Y, Sone M, Inagaki N, Kawashima A, Takeda Y, Yoneda T, Kurihara I, Itoh H, Tsuiki M, Ichijo T, Katabami T, Wada N, Sakamoto R, Ogawa Y, Yoshimoto T, Yamada T, Kawashima J, Matsuda Y, Kobayashi H, Kamemura K, Yamamoto K, Otsuki M, Okamura S, Izawa S, Okamoto R, Tamura K, Tanabe A, Naruse M; JPAS/JRAS Study Group*.
  • Journal Title: Hypertension. Volume: - Issue: 6 Pages: 1475-1482
  • DOI: 10.1161/hypertensionaha.119.14601
  • Peer Reviewed
• [Journal Article] Obesity predicts persistence of resistant hypertension after surgery in patients with primary aldosteronism (2020)
  • Author(s): Nakamaru R、Yamamoto K、Rakugi H、Akasaka H、Kurihara I、Ichijo T、Takeda Y、Katabami T、Tsuiki M、Wada N、Ogawa Y、Kawashima J、Sone M、Yoshimoto T、Okamoto R、Fujita M、Kobayashi H、Tamura K、Kamemura K、Okamura S、Kakutani M、Tanabe A、Naruse M、JPAS/JRAS Study Group
  • Journal Title: Clinical Endocrinology Volume: 93 Issue: 3 Pages: 229-237
  • DOI: 10.1111/cen.14203
  • Peer Reviewed
• [Journal Article] miRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma (2019)
  • Author(s): Nakano Yujiro、Yoshimoto Takanobu、Watanabe Ryo、Murakami Masanori、Fukuda Tatsuya、Saito Kazutaka、Fujii Yasuhisa、Akashi Takumi、Tanaka Toshihiro、Yamada Tetsuya、Naruse Mitsuhide、Ogawa Yoshihiro
  • Journal Title: European Journal of Endocrinology Volume: 181 Issue: 1 Pages: 69-78
  • DOI: 10.1530/eje-18-0882
  • Peer Reviewed