Development of disease specific therapy based on microRNA in polycystic kidney disease

• Project/Area Number: 26461618
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: Nakanishi Koichi 和歌山県立医科大学, 医学部, 准教授 (50336880)
• Co-Investigator(Kenkyū-buntansha): 吉川 徳茂 和歌山県立医科大学, 医学部, 臨床研究センター長 (10158412)
• Co-Investigator(Renkei-kenkyūsha): SHIMA Yuko 和歌山県立医科大学, 医学部, 講師 (60433364) ; HAMA Taketsugu 和歌山県立医科大学, 医学部, 博士研究員 (00508020) ; SATO Masashi 和歌山県立医科大学, 医学部, 助教 (30726716)
• Research Collaborator: MUKAIYAMA Hironobu
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 多発性嚢胞腎 / マイクロRNA / 疾患特異的治療 / 多発性のう胞腎 / マイクロアレイ / 分泌 / 増殖 / 線維化

Outline of Final Research Achievements

The purpose of this study is to elucidate contribution of microRNA (miRNA) in multiple basic pathophysiology of polycystic kidney disease and to confirm the effect of the disease specific therapy based on the modifying miRNA by treatment studies using the model animal for application to the human.
In a CPK mouse, we identified miRNA estimated to be involved in clinical condition by the miRNA microarrays of the kidney.
We confirmed biologic significance of these miRNA and examined the manifestation in blood and urine. We examined a utility of the mRNAs in the evaluation of the disease activity and explored the significance of them as the biomarker.

Research Products

• [Journal Article] ARPKDの診療指針 (2016)
  • Author(s): 中西浩一
  • Journal Title: 腎と透析 Volume: 80 Pages: 835-840
• [Journal Article] ARPKDの診断と治療 (2016)
  • Author(s): 中西浩一
  • Journal Title: 腎と透析増刊 Volume: 80増刊 Pages: 425-427
• [Journal Article] マイクロRNAに着目した多発性のう胞腎疾患特異的治療の開発 (2016)
  • Author(s): 中西浩一
  • Journal Title: 別冊BIO Clinica Volume: 5 Pages: 148-151
• [Journal Article] Insignificant impact of VUR on the progression of CKD in children with CAKUT. (2016)
  • Author(s): Ishikura K, Uemura O, Hamasaki Y, Nakai H, Ito S, Harada R, Hattori M, Ohashi Y, Tanaka R, Nakanishi K, Kaneko T, Iijima K, Honda M; Pediatric CKD Study Group in Japan in conjunction with the Committee of Measures for Pediatric CKD of the Japanese Society for Pediatric Nephrology
  • Journal Title: Pediatr Nephrol Volume: 31 Issue: 1 Pages: 105-112
  • DOI: 10.1007/s00467-015-3196-1
  • Peer Reviewed
• [Journal Article] Somatic mosaicism and variant frequency detected by next-generation sequencing in X-linked Alport syndrome. (2016)
  • Author(s): Fu XJ, Nozu K, Kaito H, Ninchoji T, Morisada N, Nakanishi K, Yoshikawa N, Ohtsubo H, Matsunoshita N, Kamiyoshi N, Matsumura C, Takagi N, Maekawa K, Taniguchi-Ikeda M, Iijima K
  • Journal Title: Eur J Hum Genet Volume: 24 Issue: 3 Pages: 387-391
  • DOI: 10.1038/ejhg.2015.113
  • Peer Reviewed
• [Journal Article] Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics (2016)
  • Author(s): Matsunoshita N, Nozu K, Shono A, Nozu Y, Fu XJ, Morisada N, Kamiyoshi N, Ohtsubo H, Ninchoji T, Minamikawa S, Yamamura T, Nakanishi K, Yoshikawa N, Shima Y, Kaito H, Iijima K
  • Journal Title: Genetics in Medicine Volume: 18 Issue: 2 Pages: 180-188
  • DOI: 10.1038/gim.2015.56
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pathogenesis of hypokalemia in autosomal dominant hypocalcemia type 1. (2016)
  • Author(s): Kamiyoshi N, Nozu K, Urahama Y, Matsunoshita N, Yamamura T, Minamikawa S, Ninchoji T, Morisada N, Nakanishi K, Kaito H, Iijima K.
  • Journal Title: Clin Exp Nephrol. Volume: 20 Issue: 2 Pages: 253-257
  • DOI: 10.1007/s10157-015-1160-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-term outcome of childhood IgA nephropathy with minimal proteinuria. (2015)
  • Author(s): Higa A, Shima Y, Hama T, Sato M, Mukaiyama H, Togawa H, Tanaka R, Nozu K, Sako M, Iijima K, Nakanishi K, Yoshikawa N.
  • Journal Title: Pediatr Nephrol. Volume: 30(12) Issue: 12 Pages: 2121-7
  • DOI: 10.1007/s00467-015-3176-5
  • Peer Reviewed
• [Journal Article] Growth impairment in children with pre-dialysis chronic kidney disease in Japan. (2015)
  • Author(s): Hamasaki Y, Ishikura K, Uemura O, Ito S, Wada N, Hattori M, Ohashi Y, Tanaka R, Nakanishi K, Kaneko T, Honda M
  • Journal Title: Clin Exp Nephrol Volume: 19 Issue: 6 Pages: 1142-1148
  • DOI: 10.1007/s10157-015-1098-y
  • Peer Reviewed
• [Journal Article] Risk factors for persistent proteinuria after a 2-year combination therapy for severe childhood IgA nephropathy (2015)
  • Author(s): Kamei K, Nakanishi K, Ito S, Ishikura K, Hataya H, Honda M, Nozu K, Iijima K, Shima Y, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 30 Issue: 6 Pages: 961-967
  • DOI: 10.1007/s00467-014-3019-9
  • Peer Reviewed
• [Journal Article] 小児期発症のADPKDとARPKD (2015)
  • Author(s): 中西浩一、吉川徳茂
  • Journal Title: 腎臓内科・泌尿器科 Volume: 1 Pages: 212-218
  • NAID: 40022582482
• [Journal Article] A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment (2015)
  • Author(s): Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, Ishikura K, Hataya H, Honda M, Ito S, Shima Y, Kaito H, Nozu K, Nakamura H, Igarashi T, Ohashi Y, Iijima K
  • Journal Title: Kidney Int Volume: 87 Issue: 1 Pages: 225-232
  • DOI: 10.1038/ki.2014.260
  • Peer Reviewed / Open Access
• [Journal Article] Renal biopsy criterion in idiopathic nephrotic syndrome with microscopic hematuria at onset (2015)
  • Author(s): Hama T, Nakanishi K, Shima Y, Sato M, Mukaiyama H, Togawa H, Hamahira K, Tanaka R, Kaito H, Nozu K, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 30 Issue: 3 Pages: 445-450
  • DOI: 10.1007/s00467-014-2946-9
  • Peer Reviewed
• [Journal Article] Cyclosporine C2 Monitoring for the Treatment of Frequently Relapsing Nephrotic Syndrome in Children: A Multicenter Randomized Phase II Trial. (2014)
  • Author(s): Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N. : Japanese Study Group of Kidney Disease in Children.
  • Journal Title: Clin J Am Soc Nephrol Volume: 9(2) Issue: 2 Pages: 271-8
  • DOI: 10.2215/cjn.13071212
  • Peer Reviewed
• [Journal Article] Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV α5 chain (2014)
  • Author(s): Hashimura Y, Nozu K, Kaito H, Nakanishi K, Fu XJ, Ohtsubo H, Hashimoto F, Oka M, Ninchoji T, Ishimori S, Morisada N, Matsunoshita N, Kamiyoshi N, Yoshikawa N, Iijima K
  • Journal Title: Kidney Int Volume: 85 Issue: 5 Pages: 1208-1213
  • DOI: 10.1038/ki.2013.479
  • Peer Reviewed
• [Journal Article] Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial (2014)
  • Author(s): Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y.
  • Journal Title: Lancet Volume: 384 Issue: 9950 Pages: 1273-1281
  • DOI: 10.1016/s0140-6736(14)60541-9
  • Peer Reviewed
• [Journal Article] Natural history of genetically proven autosomal recessive Alport syndrome (2014)
  • Author(s): Oka M, Nozu K, Kaito H, Fu XJ, Nakanishi K, Hashimura Y, Morisada N, Yan K, Matsuo M, Yoshikawa N, Vorechovsky I, Iijima K
  • Journal Title: Pediatr Nephrol Volume: 29 Issue: 9 Pages: 1535-1544
  • DOI: 10.1007/s00467-014-2797-4
  • Peer Reviewed
• [Journal Article] 多発性嚢胞腎：診断と治療に関する最新の知見 (2014)
  • Author(s): 中西浩一, 吉川徳茂
  • Journal Title: 小児科診療 Volume: 77 Pages: 757-762
• [Presentation] Differential expressions of miR-378a-3p/ADAMTS1 in cpk mice, a model of ARPKD (2016)
  • Author(s): Sato M, Koichi Nakanishi K, Hama T, Mukaiyama H, Togawa H, Yuko Shima1, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K Yoshikawa N, Suzuki H
  • Organizer: 49th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Chicago
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] cpkマウスARPKDモデルにおけるmiR-378a-3pとADAMTS1 (2016)
  • Author(s): 佐藤匡、中西浩一、浜武継、向山弘展、戸川寛子、島友子、宮嶋正康、野津寛大、長尾枝澄香、高橋久英、飯島一誠、吉川徳茂、鈴木啓之
  • Organizer: 第51回小児腎臓病学会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-07-07
• [Presentation] cpkマウスARPKDモデルにおけるmiR-378a-3p/ADAMTS1 (2016)
  • Author(s): 佐藤匡、中西浩一、浜武継、向山弘展、戸川寛子、島友子、宮嶋正康、野津寛大、長尾枝澄香、高橋久英、飯島一誠、吉川徳茂、鈴木啓之
  • Organizer: 第25回発達腎研究会
  • Place of Presentation: 東京
• [Presentation] cpkマウスARPKDモデルにおけるmiR-378a-3p/ADAMTS1 (2016)
  • Author(s): 佐藤匡、中西浩一、浜武継、向山弘展、戸川寛子、島友子、宮嶋正康、野津寛大、長尾枝澄香、高橋久英、飯島一誠、吉川徳茂、鈴木啓之
  • Organizer: 第24回のう胞性腎疾患研究会
  • Place of Presentation: 東京
• [Presentation] Dysregulation of miR-378a-3p and ADAMTS1 gene in cpk mice, a model of ARPKD. (2015)
  • Author(s): Sato M, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N
  • Organizer: 48th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] cpkマウスにおける嚢胞形成に対するsmad3ノックアウトの効果． (2015)
  • Author(s): 佐藤匡，中西浩一，浜武継，向山弘展，戸川寛子，島友子，宮嶋正康，野津寛大，長尾枝澄香，高橋久英，飯島一誠，吉川徳茂
  • Organizer: 日本小児腎臓病学会学術集会第50回記念大会
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-06-18
• [Presentation] vidence-based treatments for childhood diseases > Evidence-based Treatments for Childhood IgA Nephropathy. (2015)
  • Author(s): Nakanishi K, Yoshikawa N
  • Organizer: The 11th Asian Society for Pediatric Research
  • Place of Presentation: Osaka
  • Year and Date: 2015-04-15
  • Int'l Joint Research / Invited
• [Presentation] Ciliopathies: Mechanisms & therapies (2014)
  • Author(s): Nakanishi K
  • Organizer: The XII Asian Congress of Pediatric Nephrology
  • Place of Presentation: New Delhi, Republic of India
  • Year and Date: 2014-12-04 – 2014-12-06
  • Invited
• [Presentation] Smad3 gene deletion ameliorates cyst formation and interstitial fibrosis in cpk mouse, a model of ARPKD (2014)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Sato M, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N
  • Organizer: 47th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2014-11-11 – 2014-11-16
• [Book] 遺伝学的検査・診断・遺伝カウンセリングの上手な進め方 (2016)
  • Author(s): 中西浩一
  • Total Pages: 217
  • Publisher: 診断と治療社
• [Book] Immunoglobulin A nephropathies in children (includes HSP). "Pediatric Nephrology 7th ed." (2015)
  • Author(s): Nakanishi K, Yoshikawa N
  • Total Pages: 2730
  • Publisher: Springer, Heidelberg
• [Book] のう胞性腎疾患．「疾患からみる画像診断の進め方・読み方（小児科診療増刊号）」 (2015)
  • Author(s): 中西浩一、吉川徳茂
  • Total Pages: 348
  • Publisher: 診断と治療社、東京
• [Book] 多発性のう胞腎診療ガイドQ&A改訂第2版 (2015)
  • Author(s): 中西浩一
  • Total Pages: 184
  • Publisher: 診断と治療社
• [Book] こどもの病気遺伝について聞かれたら (2015)
  • Author(s): 中西浩一
  • Total Pages: 260
  • Publisher: 診断と治療社