Role of ADAM17 in the progression of chronic kidney disease

• Project/Area Number: 17K10144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: KAGAMI Shoji 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (00224337)
• Co-Investigator(Kenkyū-buntansha): 漆原 真樹 徳島大学, 病院, 講師 (50403689) ; 玉置 俊晃 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (80179879)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ADAM17 / レニン・アンジオテンシン系 / アンジオテンシン II / 慢性腎臓病 / 小児 / 透析 / 腎移植 / 進行 / アンジオテンシノーゲン / ACE1 / ACE2 / Ang II / 内皮細胞障害 / Angiotensin II / Glomerular cell / CKD

Outline of Final Research Achievements

Because chronic kidney disease (CKD) is chronic, progressive, and there is no effective treatment, present research was undertaken to develop new treatments and diagnostics. This research suggests that ADAM17 activity may regulate the activation of the renin-angiotensin system (RAS) involved in CKD progression. The significance of ACE1 / 2 ratio in the kidney related to RAS activity was also suggested. In the future, we will examine the mechanism of regulating RAS activity in the kidney targeting ADAM17 and develop new means to inhibit CKD progression.

Academic Significance and Societal Importance of the Research Achievements

小児の慢性腎臓病(CKD)は慢性、進行性であり、少なからず透析や腎移植が必要となる。この場合、小児の心身の発育は阻害され次世代の社会人として活躍が望めなくなる。本研究では、CKDの進行を止める、あるいは改善するための手段を開発するために行われた。その結果、ADAM17活性が、CKDの進行に関わるレニン・アンジオテンシン系(RAS)の活性化を調整している可能性が示唆された。有効な治療法がない小児CKDの進行を抑制するために、ADAM17活性を調整する手段の開発を進めていく。

Research Products

• [Journal Article] Reduction in urinary angiotensinogen levels and improvement of proteinuria by renin-angiotensin system blockade in pediatric chronic kidney disease patients with very low birth weight (2020)
  • Author(s): Yamamura-Miyazaki N, Michigami T, Satomura K, Urushihara M, Kagami S, Yamamoto K.
  • Journal Title: Pediatr Nephrol Volume: － Issue: 7 Pages: 1307-1314
  • DOI: 10.1007/s00467-020-04520-8
  • Peer Reviewed
• [Journal Article] Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome (2020)
  • Author(s): Niitsuma S, Kudo H, Kikuchi A, Hayashi T, Kumakura S, Kobayashi S, Okuyama Y, Kumagai N, Niihori T, Aoki Y, So T, Funayama R, Nakayama K, Shirota M, Kondo S, Kagami S, Tsukaguchi H, Iijima K, Kure S, Ishii N
  • Journal Title: Int Immunol Volume: 32 Pages: 283-292
  • Peer Reviewed
• [Journal Article] Expression of NADPH oxidase and production of reactive oxygen species contribute to ureteric bud branching and nephrogenesis (2019)
  • Author(s): Kondo S, Matsuura S, Ariunbold J, Kinoshita Y, Urushihara M, Suga K, Ozaki N, Nagai T, Fujioka K, Kagami S
  • Journal Title: The Journal of Medical Investigation Volume: 66 Issue: 1.2 Pages: 93-98
  • DOI: 10.2152/jmi.66.93
  • NAID: 130007638726
  • ISSN: 1343-1420, 1349-6867
  • Year and Date: 2019-02-15
  • Peer Reviewed
• [Journal Article] Enhanced angiotensinogen expression in neonates during kidney development. (2019)
  • Author(s): Shono M, Urushihara M, Suga K, Watanabe N, Saijo T, Nakagawa R, Kagami S.
  • Journal Title: Clin Exp Nephrol. Volume: 23 Issue: 4 Pages: 537-543
  • DOI: 10.1007/s10157-018-1662-3
  • Peer Reviewed
• [Journal Article] Successful treatment with voriconazole combined with amphotericin B-liposome for fluconazole-resistant pulmonary cryptococcosis after renal transplantation. (2019)
  • Author(s): Fujioka K, Nagai T, Kinoshita Y, Urushihara M, Hamasaki Y, Shishido S, Kagami S.
  • Journal Title: CEN Case Rep Volume: 8 Issue: 4 Pages: 261-265
  • DOI: 10.1007/s13730-019-00403-6
  • Peer Reviewed
• [Journal Article] Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. (2019)
  • Author(s): Kato H, Miyakawa Y, Hidaka Y, Inoue N, Ito S, Kagami S, Kaname S, Matsumoto M, Mizuno M, Matsuda T, Shimono A, Maruyama S, Fujimura Y, Nangaku M, Okada H.
  • Journal Title: Clin Exp Nephrol Volume: 23 Issue: 1 Pages: 65-75
  • DOI: 10.1007/s10157-018-1609-8
  • Peer Reviewed / Open Access
• [Journal Article] Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. (2019)
  • Author(s): Ito S, Hidaka Y, Inoue N, Kaname S, Kato H, Matsumoto M, Miyakawa Y, Mizuno M, Okada H, Shimono A, Matsuda T, Maruyama S, Fujimura Y, Nangaku M, Kagami S.
  • Journal Title: Clin Exp Nephrol Volume: 23 Issue: 1 Pages: 112-121
  • DOI: 10.1007/s10157-018-1610-2
  • Peer Reviewed / Open Access
• [Journal Article] Controversies of the classification of TMA and the terminology of aHUS. (2018)
  • Author(s): Kato H, Nangaku M, Okada H, Kagami S.
  • Journal Title: Clin Exp Nephrol. Volume: 22 Issue: 4 Pages: 979-980
  • DOI: 10.1007/s10157-017-1524-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Assessment of renal function in Japanese children with malignancies using serum cystatin C (2018)
  • Author(s): Nakamura N, Watanabe H, Okamura K, Kagami S.
  • Journal Title: The Journal of Medical Investigation Volume: 65 Issue: 3.4 Pages: 231-235
  • DOI: 10.2152/jmi.65.231
  • NAID: 130007495847
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed
• [Journal Article] (Pro)renin and (pro)renin receptor expression during kidney development in neonates. (2017)
  • Author(s): Terada T, Urushihara M, Saijo T, Nakagawa R, Kagami S.
  • Journal Title: Eur J Pediatr. Volume: 176 Issue: 2 Pages: 183-189
  • DOI: 10.1007/s00431-016-2820-9
  • Peer Reviewed
• [Journal Article] Role of the intrarenal renin-angiotensin system in the progression of renal disease. (2017)
  • Author(s): Urushihara M, Kagami S.
  • Journal Title: Pediatr Nephrol. Volume: 32 Issue: 9 Pages: 1471-1479
  • DOI: 10.1007/s00467-016-3449-7
  • Peer Reviewed
• [Presentation] 補体系と腎疾患 (2019)
  • Author(s): 香美 祥二
  • Organizer: 第122回日本小児科学会学術集会
  • Invited
• [Presentation] ラット半月体形成性腎炎モデルにおける（プロ）レニン受容体を介した病態機序と直接レニン阻害薬の治療効果 (2017)
  • Author(s): 漆原真樹、木下ゆき子、近藤秀治、永井隆、藤岡啓介、香美祥二
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 小児IgA腎症における尿中アンジオテンシン変換酵素2と糸球体病変の関係 (2017)
  • Author(s): 榊優希、漆原真樹、藤岡啓介、木下ゆき子、香美祥二
  • Organizer: 第52回日本小児腎臓病学会学術集会
• [Presentation] 溶連菌感染後急性糸球体腎炎との鑑別を要したC3腎症の1例 (2017)
  • Author(s): 田山貴広、藤岡啓介、木下ゆき子、漆原真樹、香美祥二
  • Organizer: 第34回中国四国小児腎臓病学会
• [Presentation] TSC2/PKD1 Contiguous Gene Deletion Syndrome（PKDTS）の一例 (2017)
  • Author(s): 木下ゆき子、藤岡啓介、漆原真樹、香美祥二
  • Organizer: 第47回日本腎臓学会西部学術大会