Molecular physiological analyses of renal failure in pediatric cystic renal diseases

• Project/Area Number: 19390279
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nihon University (2010); Tohoku University (2007-2009)
• Principal Investigator: KONDO Yoshiaki 日本大学, 医学部, 教授 (00221250)
• Co-Investigator(Kenkyū-buntansha): OHURA Toshihiro 東北大学, 医学系・研究科, 准教授 (10176828) ; FUJIWARA Ikuma 東北大学, 病院, 講師 (10271909) ; MUNAKATA Mitsutoshi 東北大学, 医学系・研究科, 非常勤講師 (30312573) ; UCHIDA Shinichi 東京医科歯科大学, 医歯学総合研究科, 准教授 (50262184)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA Ikuma 東北大学, 医学系・研究科, 准教授 (10271909) ; MUNAKATA Mitsutoshi 東北大学, 医学系・研究科, その他 (30312573) ; UCHIDA Shinichi 東京医科歯科大学, 医歯学総合研究科, 准教授 (50262184)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 微小単離尿細管灌流法 / 嚢胞腎 / 経上皮電位 / アポトーシス / 中心繊毛 / 管腔内圧 / ヘンレの太い上行脚 / 皮質部集合管 / ARPKD / PCKラット / 徴小単離尿細管灌流 / 抗利尿ホルモン / ヘンレループ / 慢性腎不全 / 腎尿細管 / 移植・再生医療 / 医療・福祉 / 解剖学 / 細胞・組織 / 病理学 / 腎嚢胞 / イオン輸送 / イオンチャンネル / 絨毛 / 小児末期腎不全 / 利尿薬 / 多嚢胞腎 / 集合管

Research Abstract

Among renal diseases in childhood, the rate of hereditary renal diseases such as cystic kidneys has been increased. To promote the analyses of these diseases, we conducted a series of studies including long-term in vitro microperfusion of renal tubules from normal mouse kidneys. The physiological properties of mouse cortical thick ascending limbs of Henle's loop including appearance and transepithelial voltages were not affected by 48 hours long-microperfused preparation, indicating that this new technique is applicable to many types of investigations for adaptation both rapid and slow of renal tubules to various experimental manipulations.
It has also been demonstrated the cortical thick ascending limbs of Henle's loop in PCK rat kidneys are as sensitive to vasopressin as those of tubules from normal SD rats.
Although we lost major parts of our research data due to disaster in March 2011 in Japan, our present research experiences strongly suggest that long-term in vitro microperfusion of renal tubules will give us important information on the physiology and pathophysiology of renal cystic diseases further.

Research Products

• [Journal Article] Generation and analyses of R8L barttin knockin mouse (2011)
  • Author(s): Nomura, N., Tajima, M., Sugawara, N., Morimoto, T., Kondo, Y., Ohno, M., Uchida, K., Mutig, K., Bachmann, S., Soleimani, M., Ohta, E., Ohta, A., Sohara, E., Okado, T., Rai, T., Jentsch, T. J., Sasaki, S., Uchida, S
  • Journal Title: Am J Physiol Renal Physiol Volume: 301(2)
• [Journal Article] Calcium and calcimimetics regulate paracellular Na+transport in the thin ascending limb of Henle's loop in mouse kidney (2011)
  • Author(s): Sugawara, N., Morimoto, T., Farajov, E. I., Kumagai, N., Aslanova, U. F. Rai, T., Uchida, S., Sasaki, S., Tsuchiya, S., Kondo, Y
  • Journal Title: Pflugers Arch Volume: 460(1) Pages: 197-205
• [Journal Article] Calcium and calcimimetics regulate paracellular Na^+ transport in the thin ascending limb of Henle's loop in mouse kidney (2010)
  • Author(s): Sugawara N, et al
  • Journal Title: Pflugers Arch Volume: 460 Pages: 197-205
  • Peer Reviewed
• [Journal Article] Reevaluation of glomerular charge selective protein-sieving function (2009)
  • Author(s): Saito H, Takahashi S, Nagata M, Tsuchiya T, Mugishima H, Yan K, Kondo Y, Matsuyama T, Sekine T, Igarashi T.
  • Journal Title: Pediatr Nephrol 24 (3) Pages: 609-12
  • NAID: 10024846587
  • Peer Reviewed
• [Journal Article] Stroke risk of blood pressure indices determined by home blood pressure measurement : the Ohasama study (2009)
  • Author(s): Inoue R, Ohkubo T, Kikuya M, Metoki H, Asayama K, Kanno A, Obara T, Hirose T, Hara A, Hoshi H, Totsune K, Satoh H, Kondo Y, Imai Y.
  • Journal Title: Stroke 40 (8) Pages: 2859-61
  • Peer Reviewed
• [Journal Article] Reevaluation of glomerular charge selective protein-sieving function (2009)
  • Author(s): Saito H, Takahashi S, Nagata M, Tsuchiya T, Mugishima H, Yan K, Kondo Y, Matsuyama T, Sekine T, Igarashi T.
  • Journal Title: Pediatr Nephrol 24 Pages: 609-612
  • NAID: 10024846587
  • Peer Reviewed
• [Journal Article] Stroke risk of blood pressure indices determined by home blood pressure measurement : the Ohasama study (2009)
  • Author(s): Inoue R, Ohkubo T, Kikuya M, Metoki H, Asayama K, Kanno A, Obara T, Hirose T, Hara A, Hoshi H, Totsune K, Satoh H, Kondo Y, Imai Y.
  • Journal Title: Stroke 40 Pages: 2859-2861
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor stimulates luminal K+-dependent H+excretion in medullary thick ascending limbs of Henle's loop of mouse kidney (2008)
  • Author(s): Farajov, E. I., Morimoto, T., Aslanova, U. F., Kumagai, N., Sugawara, N., Kondo, Y
  • Journal Title: Tohoku J Exp Med Volume: 216(1) Pages: 7-15
  • NAID: 10021951516
• [Journal Article] Calcium-sensing receptor stimulates luminal K+-dependent H+ excretion in medullary thick ascending limbs of Henle' s loop of mouse kidney (2008)
  • Author(s): Farajov EI, Morimoto T, Aslanova UF, Kumagai N, Sugawara N, Kondo Y.
  • Journal Title: Tohoku J Exp Med 216 (1) Pages: 7-15
  • Peer Reviewed
• [Journal Article] Calcium-sensing receptor stimulates luminal K+-dependent H+ excretion in medullary thick ascending limbs of Henle's loop of mouse kidney (2008)
  • Author(s): Farajov El, Morimoto T, Asianova UF, Kumagai N, Sugawara N. Kondo Y
  • Journal Title: Tohoku J Exp Med 216 Pages: 7-15
  • NAID: 10021951516
  • Peer Reviewed
• [Journal Article] Tonsillectomy in the treatment of pediatric Henoch-Schonlein nephritis (2007)
  • Author(s): Inoue, C. N., Chiba, Y., Morimoto, T., Nishio, T., Kondo, Y., Adachi, M., Matsutani, S
  • Journal Title: Clin Nephrol Volume: 67(5) Pages: 298-305
• [Journal Article] Molecular pathogenesis of pseudohypoaldosteronism type II : generation and analysis of a Wnk4(D561A/+) knockin mouse model (2007)
  • Author(s): Yang, S. S., Morimoto, T., Rai, T., Chiga, M., Sohara, E., Ohno, M., Uchida, K., Lin, S. H., Moriguchi, T., Shibuya, H., Kondo, Y., Sasaki, S., Uchida, S
  • Journal Title: Cell Metab Volume: 5(5) Pages: 331-44
• [Journal Article] Gestational length affects a change in the transepithelial voltage and the rNKCC2 expression pattern in the ascending thin limb of Henle's loop (2007)
  • Author(s): Nishino, M., Morimoto, T., Nishio, T., Aslanova, U. F., Farajov, E. I., Kumagai, N., Sugawara, N., Takahashi, S., Ohsaga, A., Maruyama, Y., Tsuchiya, S., Kondo, Y
  • Journal Title: Pediatr Res Volume: 61(2) Pages: 171-175
• [Journal Article] 【腎・泌尿器疾患診療マニュアル 小児から成人まで】尿細管機能異常症 腎性尿崩症 (2007)
  • Author(s): 根東義明
  • Journal Title: 日本医師会雑誌 136 (特別2)
• [Journal Article] Molecular pathogenesis of pseudohypoaldosteronism type II : generation and analysis of a Wnk4 (D 561A/+) knockin mouse model (2007)
  • Author(s): Yang SS, Morimoto T, Rai T, Chiga M, Sohara E, Ohno M, Uchida K, Lin SH, Moriguchi T, Shibuya H, Kondo Y, Sasaki S, Uchida S.
  • Journal Title: Cell Metab 5 (5) Pages: 331-44
  • Peer Reviewed
• [Journal Article] Gestational length affects a change in the transepithelial voltage and the rNKCC2 expression pattern in the ascending thin limb of Henle' s loop (2007)
  • Author(s): Nishino M, Morimoto T, Nishio T, Aslanova UF, Farajov EI, Kumagai N, Sugawara N, Takahashi S, Ohsaga A, Maruyama Y, Tsuchiya S, Kondo Y.
  • Journal Title: Pediatr Res 61 (2) Pages: 171-5
  • Peer Reviewed
• [Journal Article] Tonsillectomy in the treatment of pediatric Henoch-Schonlein nephritis (2007)
  • Author(s): Inoue CN, Chiba Y, Morimoto T, Nishio T, Kondo Y, Adachi M, Matsutani S.
  • Journal Title: Clin Nephrol 67 (5) Pages: 298-305
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A/+)knockin mouse model (2007)
  • Author(s): Sung-Sen Yang, 他
  • Journal Title: Cell Metab 5 Pages: 331-344
  • Peer Reviewed
• [Journal Article] Tonsillectomy in the treatment of pediatric Henoch-Schonlein nephritis (2007)
  • Author(s): C N Inoue, 他
  • Journal Title: Clin Nephrol 67 Pages: 298-305
  • Peer Reviewed
• [Presentation] Calcium, Magnesium, and Calcimimetics Decrease Paracellular Na+Permeability in Mouse Thin Ascending Limb of Henle's Loop (2009)
  • Author(s): Morimoto T, Sugawara N, Uchida S, Farajov EI, Kamada F, Kumagai N, Aslanova UF, Sasaki S, Tsuchiya S, Kondo Y
  • Organizer: 第42回アメリカ腎臓学会
  • Place of Presentation: San Diego
  • Year and Date: 2009-10-11
• [Presentation] Sustained In Vitro Microperfusion of Mouse Nephron Segments for Elucidating Long-Span Changes of Tubular Functions (2007)
  • Author(s): Morimoto T, Sugawara N, Kumagai N, Farajov EI, Kondo Y, Tsuchiya S
  • Organizer: 第40回アメリカ腎臓学会
  • Place of Presentation: San Francisco