Elucidation of the peritoneal regeneration mechanism by the PHSRN peptide and its clinical application

• Project/Area Number: 24591245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: TAMURA Masahito 産業医科大学, 大学病院, 准教授 (40330980)
• Co-Investigator(Kenkyū-buntansha): SERINO Ryota 産業医科大学, 大学病院, 講師 (00309957) ; MIYAMOTO Tetsu 産業医科大学, 医学部, 非常勤医師 (30611305) ; KABASHIMA Narutoshi 産業医科大学, 大学病院, 非常勤医師 (80279322)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腹膜透析 / 慢性腎不全 / 透析液 / 生体適合性 / 細胞接着 / 国際情報交換（米国）

Outline of Final Research Achievements

Long-term peritoneal dialysis (PD) is associated with the development of functional and structural alterations of the peritoneal membrane, and is eventually limited by reduced efficacy. We have shown that high glucose concentrations inhibit FAK-mediated migration of mesothelial cells, and that dialysates containing high glucose concentrations cause peritoneal damage by inhibiting wound healing of the mesothelial cell monolayer. We also showed that an integrin-activating peptide, PHSRN, ameliorates inhibitory effects of conventional peritoneal dialysis fluids on peritoneal wound healing. We elucidated that PHSRN recoveres glucose-induced inhibition of cell motility and phosphorylation of focal adhesion kinase and its downstream p130Cas.

Research Products

• [Journal Article] A Novel UMOD Gene Mutation Associated with Uromodulin-associated Kidney Disease in a Young Woman with Moderate Kidney Dysfunction. (2015)
  • Author(s): Kuma A, Tamura M, Ishimatsu N, Miyamoto T, Serino R, Ishimori S, Morisada N, Iijima K, Yamada S, Takeuchi M, Abe H, Otsuji Y.
  • Journal Title: Intern Med Volume: 54(6) Pages: 631-5
  • NAID: 130004903078
  • Peer Reviewed / Open Access
• [Journal Article] Coronary plaque progression of non-culprit lesions after culprit percutaneous coronary intervention in patients with moderate to advanced chronic kidney disease: intravascular ultrasound and integrated backscatter intravascular ultrasound study. (2015)
  • Author(s): Kashiyama K, Sonoda S, Muraoka Y, Suzuki Y, Kamezaki F, Tsuda Y, Araki M, Tamura M, Takeuchi M, Abe H, Okazaki M, Fujino Y, Otsuji Y.
  • Journal Title: Int J Cardiovasc Imaging. Volume: in press
  • Peer Reviewed
• [Journal Article] Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. (2014)
  • Author(s): Tsutsui M, Tanimoto A, Tamura M, Mukae H, Yanagihara N, Shimokawa H, Otsuji Y.
  • Journal Title: J Pharmacol Sci. Volume: 127(1) Issue: 1 Pages: 42-52
  • DOI: 10.1016/j.jphs.2014.10.002
  • Peer Reviewed
• [Journal Article] Pacing and sensing interference by air bubble surrounding the non-extended helix of intact active fixation lead. (2014)
  • Author(s): Oginosawa Y, Abe H, Ohe H, Hayashi K, Kohno R, Watabe T, Takahashi M, Fujino Y, Tamura M, Takeuchi M, Otsuji Y.
  • Journal Title: Circ J Volume: 78(12) Pages: 2862-6
  • Peer Reviewed
• [Journal Article] Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse. (2014)
  • Author(s): Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Arakaki K, Kina-Tanada M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Igarashi T, Ueno S, Matsushita M, Ishiuchi S, Masuzaki H, Ohya Y, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M.
  • Journal Title: J Mol Cell Cardiol. Volume: 77 Pages: 29-41
  • DOI: 10.1016/j.yjmcc.2014.09.021
  • Peer Reviewed / Open Access
• [Journal Article] Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis. (2014)
  • Author(s): Kuma A, Yamada S, Wang KY, Kitamura N, Yamaguchi T, Iwai Y, Izumi H, Tamura M, Otsuji Y, Kohno K.
  • Journal Title: PLoS One Volume: 9(7) Issue: 7 Pages: e103240-e103240
  • DOI: 10.1371/journal.pone.0103240
  • Peer Reviewed / Open Access
• [Journal Article] Atrial pacing site and atrioventricular conduction in patients paced for sinus node disease. (2014)
  • Author(s): Watabe T, Abe H, Kohno R, Oginosawa Y, Hayashi K, Ohe H, Tamura M, Takeuchi M, Otsuji Y.
  • Journal Title: J Cardiovasc Electrophysiol. Volume: 25(11) Issue: 11 Pages: 1224-31
  • DOI: 10.1111/jce.12476
  • Peer Reviewed / Open Access
• [Journal Article] Aortic root geometry in patients with aortic stenosis assessed by real-time three-dimensional transesophageal echocardiography. (2014)
  • Author(s): Wu VC, Kaku K, Takeuchi M, Otani K, Yoshitani H, Tamura M, Abe H, Lin FC, Otsuji Y.
  • Journal Title: J Am Soc Echocardiogr. Volume: 27(1) Issue: 1 Pages: 32-41
  • DOI: 10.1016/j.echo.2013.10.007
  • Peer Reviewed
• [Journal Article] Prognostic value of LA 10299258olumes assessed by transthoracic 3D echocardiography : comparison with 2D echocardiography (2013)
  • Author(s): Wu, VC, Takeuhi M, Kuwaki H, Iwataki M, Nagata Y, Otani K, Haruki N, Yoshitani H, Tamura M, Abe H, Negishi K, Lin FC, Otsuji Y
  • Journal Title: JACC Cardiovasc Imaging Volume: 6 Issue: 10 Pages: 1025-35
  • DOI: 10.1016/j.jcmg.2013.08.002
  • URL: http://circ.ahajournals.org/content/126/11_suppl_1/S214.long
  • Peer Reviewed
• [Journal Article] Association of seasonal variation in the prevalence of metabolic syndrome with insulin resistance. (2013)
  • Author(s): Kamezaki F, Sonoda S, Nakata S, Muraoka Y, Okazaki M, Tamura M, Abe H, Tekeuchi M, Otsuji Y.
  • Journal Title: Hypertens Res. Volume: 36(5) Issue: 5 Pages: 398-402
  • DOI: 10.1038/hr.2012.197
  • Peer Reviewed
• [Journal Article] Coronary arterial remodeling and out-stent plaque change after drug-eluting stent implantation--comparison between zotarolimus-eluting stents and paclitaxel-eluting stents. (2013)
  • Author(s): Muraoka Y, Sonoda S, Kashiyama K, Kamezaki F, Tsuda Y, Araki M, Tamura M, Takeuchi M, Abe H, Okazaki M, Otsuji Y.
  • Journal Title: Circ J. Volume: 77(2) Pages: 363-371
  • NAID: 10031138913
• [Journal Article] Immediate amelioration of mechanical pulsus alternans by adaptive servo-ventilation therapy. (2013)
  • Author(s): Haruki N, Takeuchi M, Yoshitani H, Otani K, Kuwaki H, Iwataki M, Abe H, Tamura M, Okazaki M, Otsuji Y.
  • Journal Title: Heart Lung Circ. Volume: 22(4) Issue: 4 Pages: 300-302
  • DOI: 10.1016/j.hlc.2012.08.051
• [Journal Article] Impacts of icodextrin on integrin-mediated wound healing of peritoneal mesothelial cells. (2012)
  • Author(s): Matsumoto M, Tamura M, Miyamoto T, Furuno Y, Kabashima N, Serino R, Shibata T, Kanegae K, Takeuchi M, Abe H, Okazaki M, Otsuji Y.
  • Journal Title: Life Sci Volume: 90(23-24) Issue: 23-24 Pages: 917-923
  • DOI: 10.1016/j.lfs.2012.04.036
  • Peer Reviewed
• [Presentation] Induction of Kidney Fibrosis by Fibronectin Synthesis via WNT Signaling (2014)
  • Author(s): Kuma A, Tamura M
  • Organizer: The 2014 American Society for Cell Biology Meeting
  • Place of Presentation: Philadelphia (USA)
  • Year and Date: 2014-12-07
• [Presentation] 腹膜線維化の分子機序 (2014)
  • Author(s): Tamura M
  • Organizer: 第57回日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜（神奈川、横浜）
  • Year and Date: 2014-07-04
• [Presentation] Biocompatibility and Efficacy of Icodextrin (2014)
  • Author(s): Tamura M
  • Organizer: 7th Congress of the International Society for Hemodialysis
  • Place of Presentation: Okinawa Convention Center (Okinawa, Ginowan)
  • Year and Date: 2014-04-27
  • Invited
• [Presentation] Plasma Pentraxin-3 Levels Are Associated with Risk of Nutritional Status in Hemodialysis Patients (2013)
  • Author(s): Tetsu Miyamoto, Mika Matsumoto, Hiroshi Tanaka, Emi Hasegawa, Akihiro Kuma, Yoko Fujimoto, Kenichiro Bando, Ryota Serino, Narutoshi Kabashima, Yutaka Otsuji, Masahito Tamura.
  • Organizer: Kidney Week 2013 American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Participation of WNT Protein in Acute Kidney Injury (2013)
  • Author(s): Akihiro Kuma, Tetsu Miyamoto, Ryota Serino, Narutoshi Kabashima, Masahito Tamura, Yutaka Otsuji.
  • Organizer: Kidney Week 2013 American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Effect of Adaptive Servo Ventilation Treatment for Chronic Heart Failure in Patients with Chronic Kidney Disease (2013)
  • Author(s): Akihiro Kuma, Masahito Tamura, Emi Hasegawa, Yoko Fujimoto, Kenichiro Bando, Tetsu Miyamoto, Ryota Serino, Narutoshi Kabashima, Yutaka Otsuji.
  • Organizer: Kidney Week 2013 American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Effects of Peritoneal Dialysis Using Icodextrin Dialysis Solution in Patients with Chronic Renal Failure Complicated by Refractory Congestive Heart Failure (2013)
  • Author(s): Masahito Tamura, Tetsu Miyamoto, Ryota Serino, Yumi Furuno, Kenichiro Bando, Yoko Fujimoto, Akihiro Kuma, Emi Hasegawa, Yutaka Otsuji.
  • Organizer: Kidney Week 2013 American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy with Mild Proteinuria: A Multicenter Study (2013)
  • Author(s): Hiroyuki Komatsu, Yuji Sato, Tetsu Miyamoto, Takeshi Nakata, Tomoya Nishino, Masahito Tamura, Tadashi Tomo, Masanobu Miyazaki, Shouichi Fujimoto.
  • Organizer: Kidney Week 2013 American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Protective effects of icodextrin on inter-cellular adhesion molecule-1 expression via protein kinase C in human endothelial cells (2012)
  • Author(s): Tamura M
  • Organizer: 49th ERA-EDTA Congress
  • Place of Presentation: the Palais des Congres de Paris, Paris, France
• [Presentation] High glucose peritoneal dialysate induces apoptosis through endoplasmic reticulum stress in peritoneal mesothelial cells (2012)
  • Author(s): Nakamata J, Tamura M
  • Organizer: 49th ERA-EDTA Congress
  • Place of Presentation: the Palais des Congres de Paris, Paris, France
• [Presentation] ヒト血管内皮細胞におけるProtein kinase Cを介したICAM-1発現に対するブドウ糖とicodextrinの影響の比較検討 (2012)
  • Author(s): 田村雅仁
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Book] 全人力・科学力・透析力・for the people 透析医学 (2014)
  • Author(s): 田村雅仁、宮本哲、芹野良太
  • Total Pages: 720
  • Publisher: 医薬ジャーナル社