Name of Division: Department of Homeostasis Medicine and Nephrology

 

Staff

Professor Sei Sasaki
Associate Professor Michio Kuwahara, Yoshio Terada, Shinichi Uchida
Assistant Professor Tatemitsu Rai, Hiroyuki Tamura, Seiji Inoshita

 

 

Education

  

 Department of Homeostasis Medicine and Nephrology provides the Undergraduate course and Graduate course focused on the mechanisms of maintenance of internal milieu. Those who are interested in this research area are encouraged to apply the courses.

How to Contact Us

Sei Sasaki, M. D.
Department of Homeostasis Medicine and Nephrology
Tokyo Medical and Dental University
1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

E mail:ssasaki.kid@tmd.ac.jp

Tel: 81-3-5803-5214, Fax: 81-3-5803-5215

 

Research Subjects

 1-1. Molecular cloning of transporters and channels in kidney (e.g. CLC chloride channels and AQP water channels), and functional analysis of these transporters and knock-out mice.

 1-2. Cell biological understanding of the transport proteins.

 1-3. Gene analysis of inherited kidney diseases and development of therapies.

 2-1. Analysis of the mechanisms of the glomerular nephritis

 2-2. Analysis of the mechanisms of the acute renal failure

 2-3. Regenerative medicine and gene therapy for the kidney diseases using adeno-virus vector and elctroporation method.

 

Publications

Published in 2001

  1. Akizuki N, Uchida S, Sasaki S, Marumo F: Impaired solute accumulation in inner medulla of Clcnk1-/-mice kidney. Am J Physiol. 2001; 280: F79-F87.

  2. Asai T, Kuwahara M, Sato K, Terada Y, Kurihara S, Yoneshima H, Akiba T, Marumo F: Collagen type Iα1 gene polymorphism may be associated with the rate of bone minaral density decrease in female hemodialyzed patients. Clin Exp Nephrol. 2001; 5: 234-239.

  3. Hanada S, Terada Y, Inoshita S, Lormann SM, Sasaki S, Smolenski A, Marumo F: Overexpression of protein kinase G using adenovirus inhibits cyclin E transcription and mesangial cell cycle. Am J Physiol. 2001; 280: F851- F859.

  4. Ishibashi K, Suzuki M, Sasaki S, Imai M: Identification of a new multigene four-transmembrane family (MS4A) related to CD20, HTm4 and b subunit of the high-affinity IgE receptor. Gene. 2001; 264: 87-93.

  5. Kageyama Y, Ishibashi K, Hayashi T, Xia G, Sasaki S, Kihara K: Expression of aquaporins 7 and 8 in the developing rat testis. Andrologia. 2001; 33: 165-169.

  6. Kanda E, Shimamura H, Tamura H, Uchida S, Terada Y, Sakamoto H, Kuwahara M, Akiba T, Ida T, Sasaki S, Marumo F: IgA nephropathy with complement deficiency. Internal Medicine. 2001; 40: 52-55.

  7. Kida Y, Uchida S, Miyazaki H, Sasaki S, Marumo F: Localization of mouse CLC-6 and CLC-7 mRNA and their functional complementation of yeast CLC gene mutant. Histochem Cell Biol. 2001; 115: 189-194.

  8. Kobayashi K, Uchida S, Mizutani S, Sasaki S, Marumo F: Developmental expression of CLC-K1 in the postnatal rat kidney. Histochem Cell Biol. 2001; 116: 49-56.

  9. Kobayashi K, Uchida S, Mizutani S, Sasaki S, Marumo F: Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney. J Am Soc Nephrol. 2001; 12: 1327-1334.

 10. Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S: Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet. 2001; 69: 738-748.

 11. Kyuma M, Ura N, Torii T, Takeuchi H, Takizawa H, Kitamura K, Tomita K, Sasaki S, Shimamoto K: A family with Liddle's syndrome caused by a mutation in the b subunit of the epithelial sodium channel. Clin Exp. Hypertens. 2001; 23: 471-478.

 12. Liu W, Morimoto T, Kondo Y, Iinuma K, Uchida S, Imai M: "Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates. Kidney Int. 2001; 60: 680-693.

 13. Nonomura Y, Kohsaka H, Nasu K, Terada Y, Ikeda M, Miyasaka N: Suppression of arthritis by forced expression of cyclin-dependent kinase inhibitor p21cip1 gene into the joints. Int Immunol. 2001; 13: 723-731.

 14. Owada A, Suda S, Hata T, Miyake S: The effects of bisoprolol, a selective β1-Blocker, on glucose metabolism by long-term administration in essential hypertention. Clin Exp Hypertens. 2001; 23: 305-316.

 15. Takemura T, Hino S, Kawajima H, Yanagida H, Okada M, Nagata M, Sasaki S, Barash J, Harris RC, Yoshioka K: Induction of collecting duct morphogenesis in vitro by heparin-binding epidermal growth factor-like growth factor. J Am Soc Nephrol. 2001; 12: 964-972.

 16. Terada Y, Inoshita S, Hanada S, Shimamura H, Kuwahara M, Ogawa W, Kasuga M, Sasaki S, Marumo F: Hyperosmolality activates akt and regulates apoptosis in renal tubular cells. Kidney Int. 2001; 60: 553-567.

 17. Terada Y, Okado T, Inoshita S, Hanada S, Kuwahara M, Sasaki S, Yamamoto T, Marumo F: Glucocorticoids stimulate p21CIP1 and arrest cell cycle in vitro and in anti-GBM glomerulonephritis. Kidney Int. 2001; 59: 1706-1716.

 18. Terada Y, Tanaka H, Okado T, Inoshita S, Kuwahara M, Akiba T, Sasaki S, Marumo F: Ligand-dependent-regulated erythropoietin production by naked plasmid injection and in vivo electroporation. Am J Kidney Dis. 2001; 38: S50-S53.

 19. Uchida S, Sasaki S, Marumo F: Isolation of a novel zinc finger repressor that regulates the kidney-specific CLC-K1 promoter. Kidney Int. 2001; 60: 416-421.

 20. Yamada T, Akiba T, Sasaki S: Analysis of b2-microglobulin kinetics in hemodialysis by a modified variable-volume one-compartment model. Blood Purif. 2001; 19: 388-394.

 21. Yamashita Y, Koga M, Takeda Y, Enomoto N, Uchida S, Hashimoto K, Yamano S, Dohi K, Marumo F, Sasaki S: Two sporadic cases of Liddle's syndrome caused by de novo ENaC mutations. Am J Kidney Dis. 2001; 37: 499-504.

Published in 2000

  1. Hatai T, Matsuzawa A, Inoshita S, Mochida Y, Kuroda T, Sakamaki K, Kuida K, Yonehara S, Ichijo H, Takeda K: Execution of ASK1-induced Apoptosis by the Mitochondia-dependent Caspase Activation. J.Biol.Chem 2000; 275(34): 26576-26581.

  2. Hayama A, Uchida S, Sasaki S, Marumo F: Isolation and characterization of the human CLC-5 chloride channel gene promoter. Gene 2000; 261: 353-364.

  3. Higashida T, Zeng XT, Hara M, Omori K, Sasaki S, Orikasa M, Shimizu F, Inagaki C: Immunohistochemical demonstration of Cl pump in type A intercalated cells of rat kidney. Jpn J Pharmacol 2000; 83: 233-240.

  4. Ishibashi K, Imai M, Sasaki S: Cellualr localization of aquaporin 7 in the rat kidney. Exp Nephrol 2000; 8: 252-257.

  5. Kuwahara M, Asai T, Sato K, Shinbo I, Terada Y, Marumo F, Sasaki S: Functional characterization of a water channel of the nematode Caenorhabditis elegans. Biochim Biophys Acta 2000; 1517: 107-112.

  6. Matsumoto T, Takeya M, Takuwa S, Hiquchi E, Fujimatsu A, Maeshiro H, Ito Y, Kanno K, Sasaki S, Kato H: Suppressed urinary excretion of aquaporin-2 in an infant with primary polydipsia. Pediatr Nephrol 2000; 14: 48-52.

  7. Nakashima O, Terada Y, Hanada S, Yamamoto K, Kuwahara M, Sasaki S, Marumo F: Activated STAT1 supresses proliferation of cultured rat mesangial cells. Kidney Int 2000; 57: 2249-2257.

  8. Nasu K, Kohsaka H, Nonomura Y, Terada Y, Ito H, Hirokawa K, Miyasaka N: Adenoviral Transfer of Cyclin-Dependent Kinase Inhibitor Genes Suppresses Collagen-Induced Arthritis in Mice. J Immunol 2000; 165: 7246-7252.

  9. Saito T, Ishikawa S, Ando F, Higashiyama M, Nagasaka S, Sasaki S, Saito T: Vasopressin-dependent upregulation of aquaporin-2 gene expression in glucocorticoid-deficient rats. Am J Physiol 2000; 279: F502-F508.

  10. Uchida S: Physiological role of CLC-K1 chloride channel in the kidney. Nephrol Dial Transplant 2000; 15 Suppl 6: 14-5.

  11. Uchida S: In vivo role of CLC chloride channels in the kidney. Am J Physiol Renal Physiol 2000; 279(5): F802-8.

  12. Uchida S, Marumo F: Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride channel. Exp Nephrol 2000; 8(6): 361-5.

  13. Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama K, Sasaki S, Marumo F: Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000; 20(19): 7319-7331.

  14. Yamashita Y, Hirai K, Katayama Y, Fushimi K, Sasaki S, Marumo F: Mutations in sixth transmembrane domain of AQP2 inhibit its translocation induced by vasopression. Am J Physiology 2000; 278(3): F395-405.

  15. Sasaki S: Molecular basis of organic anion and cation transport. Kidney Int 2000; 57: 1772-1773.

  16. Ishibashi K, Kuwahara M, Sasaki S: Molecular biology of aquaporins. Rev Physiol Biochem Pharmacol 2000; 141: 1-32.

Selected Publications Before 1999

  1. Michio Kuwahara, Sei Sasaki, Fumiaki Marumo. Mineralocorticoids and acidosis regulate H/HCO3 transport of intercalated cells. J. Clin. Invest. 89:1388-1394, 1992.

  2. Kiyohide Fushimi, Shinichi Uchida, Yukichi Hara, Yukio Hirata, Fumiaki Marumo, Sei Sasaki. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 361:549-552, 1993.

  3. Shinichi Uchida, Sei Sasaki, Tetsushi Furukawa, Masayasu Hiraoka, Taihei Imai, Yukio Hirata, Fumiaki Marumo. Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla. J. Biol. Chem. 268:3821-3824, 1993.

  4. Sei Sasaki, Kiyohide Fushimi, Hideuki Saito, Fumiko Saito, Shinichi Uchida, Kenichi Ishibashi, Michio Kuwahara, Tatsuro Ikeuchi, Ken-ichi Inui, Kiichiro Nakajima, Takushi X. Watanabe, Fumiaki Marumo. Cloning, characterization, and chromosomal mapping of human collecting duct aquaporin-CD. J. Clin. Invest. 93:1250-1256, 1994.

  5. Masanobu Kawasaki, Shinichi Uchida, Toshiaki Monkawa, Atsushi Miyawaki, Katsuhiko Mikoshiba, Fumiaki Marumo, Sei Sasaki. Cloning and expression of a protein kinase C-regulated chloride channel abundantly expressed in rat brain neuronal cells. Neuron 12:597-604, 1994.

  6. Kenichi Ishibashi, Sei Sasaki, Kiyohide Fushimi, Shinichi Uchida, Michio Kuwahara, Hideyuki Saito, Tetsushi Furukawa, Kiichiro Nakajima, Yumi Yamaguchi, Takashi Gojobori, Fumiaki Marumo. Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc. Natl. Acad. Sci. USA 91:6269-6273, 1994.

  7. Susumu Adachi, Shinichi Uchida, Hiroshi Ito, Mimi Hata, Michiaki Hiroe, Fumiaki Marumo, Sei Sasaki. Two isoforms of a chloride channel predominantly expressed in thick ascending limb of Henle's loop and collecting ducts of rat kidney. J. Biol. Chem. 269:17677-17683, 1994.

  8. Yoshio Terada, Kimio Tomita, M.K. Homma, Hiroshi Nonoguchi, T. Yang, T. Yamada, Sei Sasaki, Y. Yuasa, E.G. Krebs, F. Marumo. Sequential activation of raf-1 kinase, MAP kinase kinase, MAP kinase, and S6 kinase by hyperosmolality in renal cell. J. Biol. Chem. 269:31296-31301, 1994.

  9. Shinichi Uchida, Sei Sasaki, Kosaku Nitta, Keiko Uchida, Shigeru Horita, Hiroshi Nihei, Fumiaki Marumo. ClC-K1 chloride channel mediates transepithelial chloride transport in the rat thin ascending limb of Henle's loop. J. Clin. Invest. 95:104-113, 1995.

  10. Michio Kuwahara, Kiyohide Fushimi, Yoshio Terada, Liqun Bai, Fumiaki Marumo, Sei Sasaki. cAMP-dependent phosphorylation stimulates water permeability of AQP-CD water channel protein expressed in xenopus oocytes. J. Biol. Chem. 270:10384-10387, 1995.

  11. Kazuo Kanno, Sei Sasaki, Yukio Hirata, San-e Ishikawa, Kiyohide Fushimi, Setsuko Nakanishi, Daniel G. Bichet, Fumiaki Marumo. Urinary excretion of aquaporin-2 in patients with diabetes insipidus. New Engl. J. Med. 332:1540-1545, 1995.

  12. Hiroyuki Tamura, Laurent Schild, Nobuyuki Enomoto, Noriaki Matsui, Bernard C. Rossier, Sei Sasaki. Liddle disease caused by a missense mutation of b-subunit of the epithelial sodium channel gene. J. Clin. Invest. 97:1780-1784, 1996.

  13. Hisato Sakamoto, Masanobu Kawasaki, Shinichi Uchida, Sei Sasaki, Fumiaki Marumo. Identification of a new outwardly rectifying Cl channel that belongs to a subfamily of the ClC Cl channels. J. Biol. Chem. 271:10210-10216, 1996.

  14. Kiyohide Fushimi, Sei Sasaki, Fumiaki Marumo. Phosphorylation of serine 256 is required for camp-dependent regulatory exocytosis of the aquaporin-2 water channel. J. Biol. Chem. 272:14800-14804, 1997.

  15. Kenichi Ishibashi, Michio Kuwahara, Yong Gu, Yukio Kageyama, Akira Tohsaka, Fumiaki Marumo, Sei Sasaki. Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol and urea. J. Biol. Chem. 272:20782-20786, 1997.

  16. Sei Sasaki, Shinichi Uchida, Michio Kuwahara, Kiyohide Fushimi, Fumiaki Marumo. Aquaporins and ion conductance. Science 275:1490-1491, 1997.

  17. Yoshihiro Matsumura, SHinichi Uchida, Yoshiaki Kondo, Hiroaki Miyazaki, Shigeru Ko, Atsushi Hayama, Tetuji Morimoto, Wen Liu, Mikio Arisawa, Sei Sasaki, Fumiaki Marumo. Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel. Nature Genet. 21: 95-98, 1999.

 


[Graduate School, School of Medicine]

TOKYO MEDICAL AND DENTAL UNIVERSITY