Systematic identification of serine proteases involved in the progression of CKD

• Project/Area Number: 24591206
• 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 Yamanashi (2014); Kumamoto University (2012-2013)
• Principal Investigator: KITAMURA Kenichiro 山梨大学, 大学院総合研究部, 教授 (10304990)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 慢性腎不全 / セリンプロテアーゼ / タンパク尿 / 慢性腎臓病

Outline of Final Research Achievements

Few therapeutic strategies have been established for the treatment of chronic kidney diseases (CKD). Therefore, to develop a new class of the drugs is absolutely required for the patients with CKD to avoid the renal replacement therapy. Here, we demonstrated that a serine protease inhibitor significantly reduced the progression of CKD by ameliorating the glomerulosclerosis and by inhibiting the interstitial fibrosis, which suggests that serine proteases are involved in the development of the progression of CKD. In addition, we isolated plasmin as a candidate serine protease involved in the aldosterone induced renal injury.

Research Products

• [Journal Article] Low-density lipoprotein apheresis for proteinuria in lupus nephritis with intraglomerular foam cells containing cholesterol crystals. (2014)
  • Author(s): Shiraishi N, Kitamura K, Hayata M, Ogata T, Tajiri-Okamura K, Nakayama Y, Kohda Y, Tomita K, Mukoyama M.
  • Journal Title: Am J Kidney Dis. Volume: 65 Issue: 3 Pages: 490-493
  • DOI: 10.1053/j.ajkd.2014.09.028
  • Peer Reviewed
• [Journal Article] Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. (2014)
  • Author(s): Kuragano T, Matsumura O, Matsuda A, Hara T, Kiyomoto H, Murata T, Kitamura K, Fujimoto S, Hase H, Joki N, Fukatsu A, Inoue T, Itakura I, Nakanishi T.
  • Journal Title: Kidney Int. Volume: 86 Issue: 4 Pages: 845-854
  • DOI: 10.1038/ki.2014.114
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling. (2014)
  • Author(s): Uchimura K, Hayata M, Mizumoto T, Miyasato Y, Kakizoe Y, Morinaga J, Onoue T, Yamazoe R, Ueda M, Adachi M, Miyoshi T, Shiraishi N, Ogawa W, Fukuda K, Kondo T, Matsumura T, Araki E, Tomita K, Kitamura K.
  • Journal Title: Nat Commun. Volume: 11 Issue: 1 Pages: 3428-3428
  • DOI: 10.1038/ncomms4428
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and risk factor analysis of nephrosclerosis and ischemic nephropathy in the Japanese general population. (2014)
  • Author(s): Shiraishi N, Kitamura K, Kohda Y, Iseki K, Tomita K.
  • Journal Title: Clin Exp Nephrol. Volume: 18 Issue: 3 Pages: 461-468
  • DOI: 10.1007/s10157-013-0833-5
  • Peer Reviewed
• [Journal Article] The antifibrotic effect of a serine protease inhibitor in the kidney (2013)
  • Author(s): Morinaga, J., Kakizoe, Y., Miyoshi, T., Onoue, T., Ueda, M., Mizumoto, T., Yamazoe, R., Uchimura, K., Hayata, M., Shiraishi, N., Adachi, M., Sakai, Y., Tomita, K., and Kitamura, K.
  • Journal Title: Am. J. Physiol. (Renal Physiol.) Volume: 305 Issue: 2 Pages: F173-F181
  • DOI: 10.1152/ajprenal.00586.2012
  • Peer Reviewed
• [Journal Article] Urinary prostasin in normotensive individuals: correlation with the aldosterone to renin ratio and urinary sodium (2013)
  • Author(s): Olivieri, O., Chiecchi, L., Pizzolo, F., Castagna, A., Raffaelli, R., Gunasekaran, M., Guarini, P., Consoli, L., Salvagno, G., and Kitamura, K.
  • Journal Title: Hypertens. Res. Volume: 36 Issue: 6 Pages: 528-533
  • DOI: 10.1038/hr.2012.232
  • NAID: 10031189657
  • Peer Reviewed
• [Journal Article] Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension. (2013)
  • Author(s): Wakui H, Tamura K, Masuda S, Tsurumi-Ikeya Y, Fujita M, Maeda A, Ohsawa M, Azushima K, Uneda K, Matsuda M, Kitamura K, Uchida S, Toya Y, Kobori H, Nagahama K, Yamashita A, Umemura S.
  • Journal Title: Hypertension. Volume: 61(6) Issue: 6 Pages: 1203-10
  • DOI: 10.1161/hypertensionaha.111.00572
  • Peer Reviewed / Open Access
• [Journal Article] Renin Angiotensin Antagonist Nromalize Aberrant Activation of Epithelial Sodium Channels in Sodium-Sensitive Hypertension (2013)
  • Author(s): Hisako Uchio-Yamana, Shintaro Minegishi, Tomoaki Ishigami, et al.
  • Journal Title: Nephron Experimental Nephrology Volume: 122 Issue: 3-4 Pages: 95-102
  • DOI: 10.1159/000348660
  • Peer Reviewed
• [Journal Article] Effect of a serine protease inhibitor on the progression of chronic renal failure (2012)
  • Author(s): Hayata, M., Kakizoe, Y., Uchimura, K., Morinaga, J., Yamazoe, R., Mizumoto, T., Onoue, T., Ueda, M., Shiraishi, N., Adachi, M., Miyoshi, T., Sakai, Y., Tomita, K., and Kitamura, K.
  • Journal Title: Am. J. Physiol. (Renal Physiol.) Volume: 303 Issue: 8 Pages: F1126-F1135
  • DOI: 10.1152/ajprenal.00706.2011
  • Peer Reviewed
• [Journal Article] In vivo contribution of serine proteases to the proteolytic activation of γENaC in aldosterone-infused rats (2012)
  • Author(s): Uchimura, K., Kakizoe, Y., Onoue, T., Hayata, M., Morinaga, J., Yamazoe, R., Ueda, M., Mizumoto, T., Adachi, M., Miyoshi, T., Shiraishi, N., Sakai, Y., Tomita, K., and Kitamura, K.
  • Journal Title: Am. J. Physiol. (Renal Physiol.) Volume: 303 Issue: 7 Pages: F939-F943
  • DOI: 10.1152/ajprenal.00705.2011
  • Peer Reviewed
• [Journal Article] Effect of acetaminophen on progression of renal damage in adenine induced renal failure model rat. (2012)
  • Author(s): Kadowaki D, Sumikawa S, Arimizu K, Taguchi K, Kitamura K, Ishitsuka Y, Narita Y, Irie T, Maruyama T, Otagiri M, Hirata S
  • Journal Title: Life Sci. Volume: 91 Issue: 25-26 Pages: 1304-1308
  • DOI: 10.1016/j.lfs.2012.09.018
  • Peer Reviewed
• [Presentation] プロスタシンによるTLR4の発現制御を介した肝臓におけるインスリン抵抗性発症機序の解明 (2014)
  • Author(s): 内村 幸平, 早田 学, 水本 輝彦, 柿添 豊, 福田 一起, 近藤 龍也, 松村 剛, 荒木 栄一, 向山 政志, 北村 健一郎
  • Organizer: 日本心血管内分泌代謝学会
  • Place of Presentation: 横浜市開港記念会館（神奈川県横浜市）
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] ANGPTL2は腎線維化を促進する (2014)
  • Author(s): 森永 潤, 北村 健一郎, 冨田 公夫, 尾池 雄一
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Remarks] 山梨大学医学部内科学講座第３教室ホームページ
  • URL: http://yamanashi-3nai.com/