Regulation of Renal Stem Cell Number by Endothelial Cell-derived Factors

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Gunma University
• Principal Investigator: MAESHIMA AKITO 群馬大学, 医学(系)研究科(研究院), 准教授 (70431707)
• Project Period (FY): 2011 – 2013
• Keywords: 腎幹細胞 / 尿細管再生 / 血管内皮由来因子

Research Abstract

We examined the role of endothelial cell-derived factors in growth and differentiation of renal stem cell. Using BrdU labeling method, renal stem cells could be detected as BrdU-positive cells. The number of renal stem cells as well as the interstitial peritubular capillary area decreased with aging. When isolated renal stem cells were co-cultured with HUVEC, the number of renal stem cells significantly increased. HGF induced tube formation in human RPTEC. When RPTEC were co-cultured with HUVEC, tube formation was significantly enhanced. Multiple receptor tyrosine kinases were phosphorylated in RPTEC during tube formation. Collectively, these data suggest the presence of stem cell activators in the endothelial cell-derived factors.

Research Products

• [Journal Article] Involvement of N-type Ca (2+) channels in the fibrotic process of the kidney in rats (2013)
  • Author(s): Mishima K, Maeshima A, Miya M, Sakurai N, Ikeuchi H, Hiromura K, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 304(6) Pages: F665-73
  • Peer Reviewed
• [Journal Article] SIRP-alpha signaling regulates podocyte structure and function (2013)
  • Author(s): Takahashi S, Tomioka M, Hiromura K, Sakairi T, Hamatani H, Watanabe M, Ikeuchi H, Kaneko Y, Maeshima A, Aoki T, Ohnishi H, Matozaki T, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 305(6) Pages: F861-70
  • Peer Reviewed
• [Journal Article] Nephrotic Syndrome Caused by Immune-Mediated Acquired LCAT Deficiency (2013)
  • Author(s): Takahashi S, Hiromura K, Tsukida M, Ohishi Y, Sakairi T, Hamatani Ikeuchi H, Sakurai N, H, Kaneko Y, Maeshima A, Kuroiwa T, Yokoo H, Ao i T, Nagata M, Nojima Y
  • Journal Title: J Am Soc Nephrol Volume: 24 Pages: 1305-1312
  • Peer Reviewed
• [Journal Article] ワンポイントアドバイス「蛋白尿・血尿-腎臓専門医に紹介するタイミング-」 (2013)
  • Author(s): 前嶋明人
  • Journal Title: Medical Practice PDGF Volume: 30巻6号 Pages: 1098
• [Journal Article] (2013)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: 血液疾患と腎障害内科学 Volume: (第10版) Pages: 1475-1476
• [Journal Article] (2013)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: 溶血性尿毒症症候群内科学 Volume: (第10版) Pages: 1476-1477
• [Journal Article] 早期診断と治療「全身性エリテマトーデス」 (2013)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: 内科 Volume: 112巻1号 Pages: 33-37
• [Journal Article] Efficacy of tocilizumab, a humanized neutralizing antibody against interleukin-6 receptor, in progressive renal injury associated with Castleman's disease (2012)
  • Author(s): Maeshima A, Nakasatomi M, Henmi D, Yamashita S, Kaneko Y, Kuroiwa T, Hiromura K, Nojima Y
  • Journal Title: CEN Case Reports Volume: 1(1) Pages: 7-11
  • Peer Reviewed
• [Journal Article] Interleukin-1βmeasurement in stimulated whole blood cultures is useful to predict response to anti-TNF therapies in rheumatoid arthritis (2012)
  • Author(s): Kayakabe K, Kuroiwa T, Sakurai N, Ikeuchi H, Kadiombo AT, Sakairi T, Kaneko Y, Maeshima A, Hiromura K, Nojima Y
  • Journal Title: Rheumatology Volume: 51(9) (Oxford) Pages: 1639-43
  • Peer Reviewed
• [Journal Article] Interleukin-6 promotes destabilized angiogenesis by modulating angiopoietin expression in rheumatoid arthritis (2012)
  • Author(s): Kayakabe K, Kuroiwa T, Sakurai N, Ikeuchi H, Kadiombo AT, Sakairi T, Matsumoto T, Maeshima A, Hiromura K, Nojima Y
  • Journal Title: Rheumatology Volume: 51(9) (Oxford) Pages: 1571-9
  • Peer Reviewed
• [Journal Article] Hydronephrosis caused by a relapse of granulomatosis with polyangiitis (Wegener's) (2012)
  • Author(s): Umemoto A, Ikeuchi H, Hiromura K, Hamatani H, Sakurai N, Sakairi T, Matsumoto T, Maeshima A, Kuroiwa T, Nojima Y
  • Journal Title: Mod Rheumatol Volume: 22(4) Pages: 616-20
  • Peer Reviewed
• [Journal Article] Age-related decline in label-retaining tubular cells : implication for reduced regenerative capacity after injury in the aging kidney (2012)
  • Author(s): Miya M, Maeshima A, Mishima K, Sakurai N, Ikeuchi H, Kuroiwa T, Hiromura K, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 302(6) Pages: F694-702
  • Peer Reviewed
• [Journal Article] Enhancement of In Vitro Human Tubulogenesis by Endothelial Cell-derived Factors : Implications for In Vivo Tubular Regeneration after Injury (2012)
  • Author(s): Miya M, Maeshima A, Mishima K, Sakurai N, Ikeuchi H, Kuroiwa T, Hiromura K, Yokoo H, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 301(2) Pages: F387-95
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): 前嶋明人
  • Journal Title: 実地医家のための臨床検査のすすめかた・評価のしかた「腎・泌尿器疾患I.症候から診断へ」 Medical Practice Volume: (2012年臨時増刊号) Pages: 78-84
  • Peer Reviewed
• [Journal Article] 各種病態にみられる腎障害「血栓性血小板減少性紫斑病」 (2012)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: 別冊日本臨床新領域別症候群シリーズNo.18腎臓症候群 Volume: (第2版) Pages: 405−408
• [Journal Article] (2012)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: 腎・透析診療最新ガイドライン「アミロイド腎」 Pages: 41-44
• [Journal Article] ループス腎炎の治療と予後 (2012)
  • Author(s): 前嶋明人、野島美久
  • Journal Title: リウマチ科 Volume: 47巻5号 Pages: 481-487
• [Journal Article] Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis (2011)
  • Author(s): Takahashi S, Hiromura K, Sakurai N, Matsumoto T, Ikeuchi H, Maeshima A, Kaneko Y, Kuroiwa T, Nojima Y
  • Journal Title: Mod Rheumatol Volume: 21(3) Pages: 282-9
  • Peer Reviewed
• [Journal Article] Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo (2011)
  • Author(s): Sakairi T, Hiromura K, Takahashi S, Hamatani H, Takeuchi S, Tomioka M, Maeshima A, Kuroiwa T, Nojima Y
  • Journal Title: Nephrology Volume: 16(1) (Carlton) Pages: 76-86
  • Peer Reviewed
• [Journal Article] Treatment with valsartan stimulates endothelial progenitor cells and renal label-retaining cells in hypertensive rats (2011)
  • Author(s): Yoshida Y, Fukuda N, Maeshima A, Yamamoto C, Matsumoto T, Ueno T, Nojima Y, Matsumoto K, Soma M
  • Journal Title: J Hypertens Volume: 29(1) Pages: 91-101
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor binding protein-related protein 1 is expressed in rheumatoid synovium and regulates synovial fibroblast proliferation (2011)
  • Author(s): Sakurai N, Kuroiwa T, Kayakabe K, Matsumoto T, Maeshima A, Hiromura K, Nojima Y
  • Journal Title: Mod Rheumatol Volume: 21(1) Pages: 63-72
  • Peer Reviewed
• [Presentation] RISK FACTORS FOR MORTALITY IN PATIENTS WITH LUPUS NEPHRITIS : A LONG-TERM STUDY AT A SINGLE CENTER IN JAPAN (2013)
  • Author(s): Kayakabe K, Ikeuchi H, Hiromura K, Kadiombo AT, Sakurai N, Sakairi T, Kaneko Y, Maeshima A, Nojima Y
  • Organizer: Annual European Congress of Rheumatology 2013
  • Place of Presentation: Madrid
  • Year and Date: 20130612-15
• [Presentation] Quantitative evaluation of epithelial-mesenchymal transition during renal fibrosis (2013)
  • Author(s): Nakasatomi M, Maeshima A, Mishima K, Sakurai N, Ikeuchi H, Sakairi T, Kaneko Y, Hiromura K, Nojima Y
  • Organizer: World Congress of Nephrology 2013
  • Place of Presentation: Hongkong
  • Year and Date: 20130531-0603
• [Presentation] 腎線維化におけるN型カルシウムチャネルの役割 (2013)
  • Author(s): 前嶋明人
  • Organizer: 群馬CKDセミナー
  • Place of Presentation: 群馬
  • Year and Date: 2013-11-21
  • Invited
• [Presentation] 腎線維化におけるN型Caチャネルの役割 (2013)
  • Author(s): 前嶋明人
  • Organizer: 群馬N型カルシウムチャネル研究会
  • Place of Presentation: 群馬
  • Year and Date: 2013-09-10
  • Invited
• [Presentation] 腎線維化におけるN型Caチャネルの役割 (2013)
  • Author(s): 前嶋明人
  • Organizer: 第4回交感神経と高血圧研究会
  • Place of Presentation: 群馬
  • Year and Date: 2013-06-13
  • Invited
• [Presentation] Mixed Lesion of Membranous (Class V) and Proliferative (Class III/IV) Lupus Nephritis Predicts Poor Renal Prognosis (2012)
  • Author(s): Ikeuchi, H, Hiromura K, Takahash S, Mishima K, Sakurai N, Sakairi T, Kaneko Y, Maeshima A, Nojima Y
  • Organizer: 45th American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20121031-1105
• [Presentation] Efficacy and Safety of Multitarget Therapy by Combination with Tacrolimus, Mycophenolate Mofetil and Steroid in Patients with Active Lupus Nephritis (2012)
  • Author(s): Ikeuchi, H, Hiromura K, Takahash S, Mishima K, Sakurai N, Sakairi T, Kaneko Y, Maeshima A, Nojima Y
  • Organizer: 45th American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20121031-1105
• [Presentation] Expression of a Novel Stress-Inducible Protein, Sestrin 2, in Rat Glomerular Parietal Epithelial Cells (PECs) (2012)
  • Author(s): Hamatani H, Hiromura K, Sakairi T, Takahash S, Maeshima A, Ohse T, Pippin JW, Shankland SJ, Nojima Y
  • Organizer: 45th American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20121031-1105
• [Presentation] Majority of Proximal Tubular Cells in the Outer Medulla are Slow-cycling and Equally Contribute to Tubular Regeneration after Renal Ischemia (2012)
  • Author(s): Maeshima A, Miya M, Mishima K, Sakurai N, Ikeuchi H, Sakairi T, Kaneko Y, Hiromura K, Nojima Y
  • Organizer: 10th International Society of Stem Cell Research 2012
  • Place of Presentation: Yokohama
  • Year and Date: 20120613-16
• [Presentation] 腎尿細管の修復・再生メカニズム (2012)
  • Author(s): 前嶋明人
  • Organizer: 第16回腎間質障害研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-08
  • Invited
• [Presentation] 腎再生医療の可能性と方向性 (2012)
  • Author(s): 前嶋明人
  • Organizer: 第11回腎保護・再生研究会
  • Place of Presentation: 神戸
  • Year and Date: 2012-07-13
  • Invited
• [Presentation] 腎再生医学に関する最近の知見 (2012)
  • Author(s): 前嶋明人
  • Organizer: 第16回埼玉腎臓病若手研究会
  • Place of Presentation: さいたま
  • Year and Date: 2012-05-19
  • Invited
• [Presentation] A Novel Case of Nephrotic Syndrome Caused by Immune-Mediated Severe LCAT Deficiency (2011)
  • Author(s): Takahashi S, Hiromura K, Tsukida M, Ohishi Y, Hamatani H, Sakurai N, Sakairi T, Ikeuchi H, Maeshima A, Kuroiwa T, Nagata M, Nojima Y
  • Organizer: 44th American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111110-13
• [Presentation] Transforming Growth Factor (TGF)-β1 Induced DNA Methylation of Wilms'Tumor Suppressor Gene (WT1) Promoter in Human Podocytes (2011)
  • Author(s): Hamatani H, Hiromura K, Sakairi T, Takahashi S, Ikeuchi H, Maeshima A, Nojima Y
  • Organizer: 44th American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111110-13
• [Presentation] Pro-Inflammatory Cytokine Measurement in Whole Blood Cultures Stimulated with Lipopolysaccharide Predicts Treatment Outcomes of Patients with Rheumatoid Arthritis Treated with Biologics (2011)
  • Author(s): Kayakabe K, Kuroiwa T, Sakurai N, Ikeuchi H, Anastasie KT, Sakairi T, Maeshima A, Hiromura K, Nojima Y
  • Organizer: 77th American College of Rheumatology
  • Place of Presentation: Chicago, USA
  • Year and Date: 20111105-09
• [Presentation] 腎臓の線維化と再生を担う細胞群を探る「腎尿細管の修復・再生メカニズム」 (2011)
  • Author(s): 前嶋明人
  • Organizer: 第54回日本腎臓学会総会
  • Place of Presentation: 横浜 (ワークショップ)
  • Year and Date: 20110615-17
• [Presentation] INTERLEUKIN-6 PROMOTES PATHOLOGICAL ANGIOGENESIS BY MODULATING ANGIOPOIETIN EXPRESSION IN RHEUMATOID ARTHRITIS (2011)
  • Author(s): Kayakabe K, Kuroiwa T, Sakurai N, Ikeuchi H, Anastasie KT, Sakairi T, Maeshima A, Hiromura K, Nojima Y
  • Organizer: Annual European Congress of Rheumatology 2011
  • Place of Presentation: London, UK
  • Year and Date: 20110525-28