Omics analysis of macrophage-related molecules for urolithiasis dissolution therapy

• Project/Area Number: 16K11054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Taguchi Kazumi 名古屋市立大学, 大学院医学研究科, 研究員 (00595184)
• Co-Investigator(Kenkyū-buntansha): 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 安井 孝周 名古屋市立大学, 大学院医学研究科, 教授 (40326153) ; 戸澤 啓一 名古屋市立大学, 大学院医学研究科, 教授 (40264733) ; 岡田 淳志 名古屋市立大学, 大学院医学研究科, 准教授 (70444966) ; 濱本 周造 名古屋市立大学, 大学院医学研究科, 講師 (80551267)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 尿路結石症 / マクロファージ / 結晶貪食 / 溶解治療 / M1 / M2 / 結石モデルマウス / flow cytometry / マルチプレックス解析 / 遺伝子発現解析 / マイクロアレイ / 尿路結石 / 腎乳頭部 / 腎乳頭石灰化 / オミックス解析

Outline of Final Research Achievements

We previously reported that the relationship between renal stone formation and macrophage. In this study, we focused on the phenotype of macrophage, in particular, M2-type anti-inflammatory macrophages and performed functional analyses for stone formation.
The M2-type macrophage was less expressed in renal papilla plaque, a precursor of stone, as well as urine sample in kidney stone patients compared with controls. More importantly, the treatment of M2-type macrophage in a stone model mouse demonstrated the suppression effect for stone development. These results indicate that potential therapeutic use of M2-type macrophage for kidney stone disease.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで有効な薬物治療がなかった尿路結石症に対して、M2型マクロファージによる結晶貪食作用を利用し、結石溶解治療への可能性を示したものである。この研究成果は、再発予防に有用なだけでなく、将来的に現在主流となっている外科的治療に取って代わるものとなりうる可能性を秘めている。尿路結石症の生涯罹患率が今や１０%に達成している現状を鑑みると、治療法の躍進につながる発見と考えられる。

Research Products

• [Int'l Joint Research] University of California San Francisco(米国)
• [Int'l Joint Research] University of California San Francisco(米国)
• [Int'l Joint Research] University of California San Francisco(米国)
• [Journal Article] Helper T-cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques. (2019)
  • Author(s): Taguchi K, Hamamoto S, Okada A, Sugino T, Unno R, Ando R, Gao B, Tozawa K, Kohri K, Yasui T
  • Journal Title: Int J Urol Volume: - Issue: 6 Pages: 670-677
  • DOI: 10.1111/iju.13950
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model (2019)
  • Author(s): Okada Atsushi、Ando Ryosuke、Taguchi Kazumi、Hamamoto Shuzo、Unno Rei、Sugino Teruaki、Tanaka Yutaro、Mizuno Kentaro、Tozawa Keiichi、Kohri Kenjiro、Yasui Takahiro
  • Journal Title: Clinical and Experimental Nephrology Volume: 23 Issue: 5 Pages: 710-716
  • DOI: 10.1007/s10157-019-01693-x
  • Peer Reviewed
• [Journal Article] Optimizing RNA Extraction of Renal Papilla Biopsy Tissue in Kidney Stone Formers: A New Methodology for Genomic Study. (2017)
  • Author(s): Taguchi K, Usawachintachit M, Hamamoto S, Unno R, Tzou DT, Sherer BA, Wang Y, Okada A, Stoller ML, Yasui T, Chi T.
  • Journal Title: J Endourol Volume: 31 Issue: 9 Pages: 922-929
  • DOI: 10.1089/end.2017.0320
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic Risk Factors for Idiopathic Urolithiasis: A Systematic Review of the Literature and Causal Network Analysis. (2017)
  • Author(s): Taguchi Kazumi, Yasui Takahiro, Milliner Schmautz Dawn, Hoppe Bernd, Chi Thomas
  • Journal Title: EUROPEAN UROLOGY FOCUS Volume: 3 Issue: 1 Pages: 71-81
  • DOI: 10.1016/j.euf.2017.04.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Animal models of urinary stone disease.Animal models of urinary stone disease. (2017)
  • Author(s): Tzou DT, Taguchi K, Chi T, Stoller ML.
  • Journal Title: Int J Surg Volume: 35 Pages: 596-606
  • DOI: 10.1016/j.ijsu.2016.11.018
• [Journal Article] Genome-wide gene expression profiling of Randall's plaques in calcium oxalate stone formers (2017)
  • Author(s): Taguchi K, Hamamoto S, Okada A, Unno R, Kamisawa H, Naiki T, Ando R, Mizuno K, Kawai N, Tozawa K, Kohri K, Yasui T
  • Journal Title: J Am Soc Nephrol Volume: 28 Issue: 1 Pages: 333-347
  • DOI: 10.1681/asn.2015111271
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development (2017)
  • Author(s): 70.Taguchi Kazumi, Okada Atsushi, Hamamoto Shuzo, Unno Rei, Moritoki Yoshinobu, Ando Ryosuke, Mizuno Kentaro, Tozawa Keiichi, Kohri Kenjiro, Yasui Takaihro
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 35167-35167
  • DOI: 10.1038/srep35167
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 腎乳頭部Randall's Plaqueの遺伝子発現解析からみる分子標的治療の可能性 (2018)
  • Author(s): 田口 和己、濵本 周造、岡田 淳志、安井 孝周
  • Organizer: 第83回日本泌尿器科学会東部総会
  • Invited
• [Presentation] Pro-inflammatory and immune-active responses predominantly leading to Randall’s plaque formation on calcium phosphate stone (2018)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Unno Rei, Tanaka Yutaro, Sugino Teruaki, Ando Ryosuke, Okada Atsushi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Discovery of fatty acid binding protein 4 as an essential molecule for the development of kidney stones: A new understanding of the relationship between obesity and nephrolithiasis. (2018)
  • Author(s): Taguchi Kazumi, Chen L, Usawachintachit Manint, Hamamoto Shuzo, Kang M, Unno Rei, Tzou David, Sherer Benjamin, Yasui Takahiro, Ho S, Stoller Marshall, Chi Thomas
  • Organizer: 4th Anuual EAU Congress
  • Int'l Joint Research
• [Presentation] Prevention of recurrent urolithiasis up to date. (2018)
  • Author(s): Taguchi Kazumi
  • Organizer: The 33rd Annual EAU Congress
  • Int'l Joint Research / Invited
• [Presentation] Optimizing RNA extraction of renal papilla biopsy tissue in kidney stone formers: a new methodology for genomic study. (2017)
  • Author(s): Taguchi Kazumi, Usawachintachit Manint, Tzou T David, Hamamoto Shuzo, Sherer A Benjamin, Stoller L Marshall, Yasui Takahiro, Chi Thomas
  • Organizer: The 35th World Congress of the Endourology
  • Int'l Joint Research
• [Presentation] カルシウム結石溶解へ挑戦 (2017)
  • Author(s): 田口 和己、濵本 周造、岡田 淳志、戸澤 啓一、安井 孝周
  • Organizer: 日本尿路結石症学会第27回学術集会
  • Invited
• [Presentation] 尿路結石形成機構の解明と溶解治療への挑戦 (2017)
  • Author(s): 田口 和己、濵本 周造、岡田 淳志、安井 孝周
  • Organizer: 第67回日本泌尿器科学会中部総会
  • Invited
• [Presentation] Discovery of Randall’s plaque gene expression profiling in calcium oxalate stone formers by immunohistochemical genome-wide analysis. (2016)
  • Author(s): Taguchi K, Hamamoto S, Sugino T, Unno R, Hirose M, Ando R, Okada A, Tozawa K, Chi T, Stoller ML, Kohri K, Yasui T
  • Organizer: 13th International Symposium on Urolithiasis
  • Place of Presentation: 幕張メッセ（千葉県千葉市)
  • Year and Date: 2016-07-19
  • Int'l Joint Research
• [Presentation] Discovery of Randall’s plaque gene expression profiling in calcium oxalate stone formers by immunohistochemical genome-wide analysis. (2016)
  • Author(s): Taguchi K, Unno R, Kamisawa H, Naiki T, Hamamoto S, Ando R, Okada A, Tozawa K, Kohri K, Yasui T
  • Organizer: American Urological Association Annual Meeting 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Different roles of M1/M2 macrophage phenotype for renal crystal formation. (2016)
  • Author(s): Taguchi K, Unno R, Fujii Y, Hirose Y, Usami M, Hamamoto S, Ando R, Okada A, Itoh Y, Tozawa K, Kohri K, Yasui T
  • Organizer: American Urological Association Annual Meeting 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Rising star report マクロファージによる結石溶解療法。 (2016)
  • Author(s): 田口 和己、濵本 周造、安藤 亮介、岡田 淳志、戸澤 啓一、郡 健二郎、安井 孝周
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センターほか（宮城県仙台市）
  • Year and Date: 2016-04-23
  • Invited
• [Book] マクロファージと尿路結石。腎臓内科・泌尿器科 (2016)
  • Author(s): 田口 和己、岡田 淳志、安井 孝周
  • Publisher: 科学評論社