埼玉大学
脳末梢科学研究センター
Brain and Body System Science Institute (BBSSI), Saitama University

ー学内外の知を終結した、戦略的研究拠点ー

組織・構成

個人プロフィール

氏名 坂井 貴文
所属部門 脳末梢機能連関研究部門
役職 兼任教員 理工学研究科教授

略歴

1977 群馬大学教育学部卒業
1978 群馬大学大学院教育専攻科修了
1992 博士(医学)群馬大学 , Effect of passive immunization to gonadotropin-releasing hormone(GnRH)using antiserum on mitotic activity of gonadotrophs in castrated rats.
1988 - 1991 群馬大学内分泌研究所文部技官
1991 - 1994 群馬大学内分泌研究所助手
1994 - 1995 埼玉大学理学部講師
1995 - 2003 埼玉大学理学部助教授
1996 - 2003 埼玉大学理工学研究科助教授
1998 - 1999 米国国立衛生研究所(National Institutes of Health)国立がん研究所客員研究員
2003 - 現在 埼玉大学理工学研究科教授
2003 - 現在 埼玉大学理学部教授

研究テーマ

(1) 消化管ホルモンを中心とした脳-腸相関の研究

ghrelinは主に胃より分泌され、成長ホルモン分泌や摂食亢進作用などを通して、生体のエネルギー消費と成長を制御している。近年の研究から、グレリンはヒトで消化管運動亢進作用を持つことが報告されているが、その作用機構は不明である。一方、モチリンは十二指腸より空腹時に放出されるホルモンであり、胃より分泌されるグレリンと高い相同性を有し、ファミリーを形成している。その生理作用として空腹時の消化管蠕動運動を惹起することが知られているが、作用機構は不明のままである。本研究では、フォーストランスデューサーを逢着した無麻酔・無拘束スンクスを用いたin vivo実験とマグヌス管によるin vitro実験により、モチリンおよびグレリンの分泌機構および消化管運動刺激機構の解明を生理学的手法を用いて行う。加えて、両ホルモンおよび受容体の発現動態や発現分布等を形態学的、分子生物学的研究により明らかにするとともに、グレリンおよびモチリンの分泌刺激機構をin vivoin vitro実験で検討する。これらの研究を通じて、消化管ホルモン作用の脳-腸相関を明らかにする。

(2) 消化管関連病態モデルの作成とtranslational研究

スンクスを用いて、糖尿病、肥満、ストレス性胃腸障害等の病態モデルを作成し、消化管運動への影響およびその作用機構の研究を行う。また、製薬企業との共同研究として漢方薬を含む各種薬剤のこれら病態に対する効果を検討するなどのtranslational研究を行う。

(3) 下垂体発生の研究

近年、細胞増殖・分化あるいは器官形成研究のモデルとして下垂体が注目され、それに係る因子の同定が行われている。本研究室では下垂体発生研究に従来使われていたマウスに加え、特徴的な下垂体細胞分布様式を持つニワトリを用いて下垂体発生機構の解明を行い、従来定説とされている下垂体分化機構とは異なるメカニズムの存在を明らかにしている。本研究では、形態学的研究および遺伝子導入研究を行い、ニワトリ下垂体形成に関わる因子の発現とそれらの相互作用について調べる。

(4) 下垂体隆起部の研究

下垂体前葉の前方に正中隆起を包むようにして存在する下垂体隆起部は、高密度のメラトニン受容体が存在することで近年注目を集めつつあるが、その生理的役割や構成する細胞の性質などは不明な点が多い。我々は下垂体隆起部の生理作用を明らかにする事を目的として一連の研究を行っており、今までに隆起部に発現するホルモンを含む諸因子や発生過程の解析結果を報告してきた。本研究において、隆起部に発現する遺伝子を網羅的に解析することにより、隆起部ホルモンの発現・分泌機構を明らかにする。また、隆起部から産生されるαGSUの下垂体前葉細胞に対する作用を検討することで、隆起部の生理的意義に迫る。

(5) ペプチドアプタマーの創製

近年、タンパク質、ペプチドや生体小分子に結合する人工的なペプチド(ペプチドアプタマー)の創製が盛んに行われ、創薬への応用が期待されている。本研究では、製薬企業との共同研究として、in vitro virus (IVV)法を用いた受容体に対するペプチドアプタマー創製に加えて、既に同定されているアプタマー候補の解析を行う。

研究のキーワード

ghrelin(グレリン);モチリン;スンクス;空腹期収縮;下垂体;ペプチドアプタマー

これまでの主要な業績

  1. Akira Kawashima, Kazunari Tanigawa, Takeshi Akama, Huhehasi Wu, Mariko Sue, Aya Yoshihara, Yuko Ishido, Kouji Kobiyama, Fumihiko Takeshita, Ken J. Ishii, Hisashi Hirano, Hiroaki Kimura, Takafumi Sakai, Norihisa Ishii, and Koichi Suzuki: Fragments of Genomic DNA Released by Injured Cells Activate Innate Immunity and Suppress Endocrine Function in the Thyroid. Endocrinology 152(4), 1702-1712, 2011
  2. Mohammed Naimuddin, Suzuko Kobayashi, Chihiro Tsutsui, Masayuki Machida, Naoto Nemoto, Takafumi Sakai and Tai Kubo: Directed evolution of a three-finger neurotoxin by using cDNA display yields antagonists as well as agonists of interleukin-6 receptor signaling. Molecular Brain 4:02, 16 pages, 2011
  3. Takamichi Hirata, Naoki Takeda, Chihiro Tsutsui, Kanako Koike, Yuichi Shimatani, Takafumi Sakai, Masahiro Akiya, and Akira Taguchi: Measurement of Contractile Activity in Small Animal's Digestive Organby Carbon Nanotube-Based Force Transducer. Jpn. J. Appl. Phys 50, 030210 (3 pages 2011
  4. Sakahara S, Xie Z, Koike K, Hoshino S, Sakata I, Oda S, Takahashi T, Sakai T: Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus). American journal of physiology. Regulatory, integrative and comparative physiology 299(4), Epub ahead of print, 2010
  5. Sakata I, Sakai T: Ghrelin cells in the gastrointestinal tract. International Journal of Peptides Article ID 945056, 7 pages, 2010
  6. Ishida Y, Sakahara S, Tsutsui C, Kaiya H, Sakata I, Oda S, Sakai T: Identification of ghrelin in the house musk shrew (Suncus murinus): cDNA cloning, peptide purification and tissue distribution. Peptides 30, 982-90, 2009
  7. Tsutsui C, Kajihara K, Yanaka T, Sakata I, Itoh Z, Oda S, Sakai T: House musk shrew (Suncus murinus, order: Insectivora) as a new model animal for motilin study. Peptides 30, 318-329, 2009
  8. Zheng Z, Sakai T: Characteristic features of ghrelin cells in the gastorintestinal tract and the regulation of tsomach ghrelin expressin and production. World J Gastoreterol 14, 6306-6311, 2008
  9. Takagi H, Nagashima K, Inoue M, Sakata I and Sakai T: Detailed analysis of formation of the chicken pituitary primordium in early embryonic development. Cell Tissue Research 333, 417-426, 2008
  10. Yamamoto I, Kaiya H, Tsutsui C, Sakai T, Tsukada A, Miyazato M, Tanaka M: Primary structure, tissue distribution, and biological activity of chicken motilin receptor. Gen Comp Endocrinol 156, 509-514, 2008
  11. T. Hirata S, Amiya M, Akiya O, Takei T, Sakai T, Nakamura J, Kawamura-Tsuzuku T, Yamamoto R, Hatakeyama: Chemical modification of carbon nanotube based bio-nanosensor by plasma activation. Japanese Journal of Applied Physics 47(4), 2068-2071 2008
  12. Jun Zheng, Hiroyasu Takagi, Chihiro Tsutsui, Akihito Adachi, Takafumi Sakai: Hypophyseal corticosteroids stimulate somatotrope differentiation in the embryonic chicken pituitary gland. Histochemistry and Cell Biology 129(3), 357-365 2008
  13. Zheng Zhao, Ichiro Sakata, Yusuke Okubo, Kanako Koike, Kenji Kangawa, Takafumi Sakai: Gastric leptin, but not estrogen and somatostatin, contributes to the elevation of ghrelin mRNA expression level in fasted rats. Journal of Endocrinology 196(3), 529-538 2008
  14. Yusuke Okubo, Kazuto Ikemoto, Kanako Koike, Chihiro Tsutsui, Ichiro Sakata, Osamu Takei, Akihito Adachi, Takafumi Sakai: DNA introduction into living cells by water droplet impact with an electrospray process. Angewandte Chemie-International Edition 47(8), 1429-1431 2008
  15. Suzuki M, Ito Y, Sakata I, Sakai T, Husimi Y, Douglas KT: Caspase-3 sensitive signaling in vivo in apoptotic HeLa cells by chemically engineered intramolecular fluorescence resonance energy transfer mutants of green fluorescent protein. Biochem Biophys Res Commun 330, 54-60 2005
  16. Yamato M, Sakata I, Wada R, Kaiya H, Sakai T: Exogenous administration of octanoic acid accelerates octanoylated ghrelin production in the proventriculus of neonatal chicks. Biochem Biophys Res Commun 333, 583-59 2005
  17. Aramaki S, Sato F, Soh T, Yamauchi N, Sakai T, Hattori MA: Temporal and spatial expression of TGF-beta2 in chicken somites during early embryonic development. J Exp Zoolog A Comp Exp Biol. 303, 323-30 2005
  18. Zheng J, Nakamura K, Maseki Y, Geelissen SM, Berghman LR, Sakai T: Independent differentiation of mammotropes and somatotropes in the chicken embryonic pituitary gland Analysis by cell distribution and attempt to detect somatomammotropes. Histochem Cell Biol. 1-11 2005
  19. Takahashi A, Nakata O, Kosugi T, Kako K, Sakai T, Ito M, Takamatsu N, Shiba T, Sower SA, Kawauchi H: Promoter activity of sea lamprey proopiocortin and proopiomelanotropin genes in AtT-20/D16v cells. Gen Comp Endocrinol. 144, 182-7 2005
  20. Maseki Y, Nakamura K, Iwasawa A, , Zheng J, Inoue K, Sakai T: Development of gonadotropes in the chicken embryonic pituitary gland. Zoolog. Sci. 21(4), 435-44 2004
  21. Matsubara M, Sakata I, Wada R, Yamazaki M, Inoue K, Sakai T: Estrogen modulates ghrelin expression in the female rat stomach. Peptides 25(2), 289-97 2004
  22. Nakamura K, Iwasawa A, Kidokoro H, Komoda M, Zheng J, Maseki Y, Inoue K, Sakai T: Development of thyroid-stimulating hormone beta subunit-producing cells in the chicken embryonic pituitary gland. Cells Tissues Organs 177, 21-8 2004
  23. Sakata I, Mori T, Kaiya H, Yamazaki M, Kangawa K, Inoue K, Sakai T: Localization of ghrelin-producing cells in the stomach of the rainbow trout (Oncorhynchus mykiss). Zoolog Sci. 21, 757-62 2004
  24. Yamazaki M, Kobayashi H, Tanaka T, Kangawa K, Inoue K, Sakai T: Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells depends on intracellullar and extracellular ca sources. J. Neuroendocrinol. 16, 825-31 2004
  25. Kaiya H, Sakata I, Kojima M, Hosoda H, Sakai T, Kangawa K: Structural determination and histochemical localization of ghrelin in the red-eared slider turtle, Trachemys scripta elegans. Gen. Comp. Endocrinol. 138, 50-7 2004
  26. Fujiwara K, Maruyama M, Usui K, Sakai T, Matsumoto H, Hinuma S, Kitada C, Inoue K: Appearance of prolactio-releasing peptide-producing neurons in the area postrema of adrenalectomized rats. Neurosci. Lett. 338, 127-30 2003
  27. R. Wada, I. Sakata, H. Kaiya, K. Nakamura. Y. Hayashi, K. Kangawa and T. Sakai: Existence of ghrelin-immunopositive and expressing cells in proventriculus of the hatching and adult chicken. Regul. Pept. 111:123-28 2003
  28. Sakata I., M. Yamazaki, K. Inoue, Y. Hayashi, K. Kangawa, T. Sakai: Growth hormone secretagogue receptor expression in the cells of the stomach-projected afferent nerve in the rat nodose ganglion. Neurosci. Lett. 342, 183-86 2003
  29. Tomizawa K., S. Ogawa, T. Kato, M. Watanabe, I. Sato, T. Ihara, T. Sakai, M. Hattori, K. Inoue, S. Ueda, M. Kikuchi, J. Mori and Y. Kato: Production and Characterization of an Antiserum against Recombinant Porcine Follicle Stimulating Hormone. J. Reprod. Dev. 48, 131-36 2002
  30. Suzuki K., IE. Royaux, LA. Everett, A. Moriaoki, S. Suzuki, K. Nakamura, T. Sakai, R. Katoh, ED. Green and LD. Kohn: Expression of PDS/Pds, the Pendred Syndrome Gene, in Endometrium. Journal of Crinical Endocrinology & Metabolism 87(2), 938 2002
  31. Sakata I., T. Tanaka, M. Matsubara, M. Yamazaki, S. Tani, Y. Hayashi, K. Kangawa and T. Sakai: Postnatal Changes in Ghrelin mRNA Expression and inGhrelin-producing Cells in the Rat Stomach. J. Endocrinology 174, 464-71 2002
  32. Yamazaki M., K. Nakamura, H. Kobayashi, M. Matsubara, Y. Hayashi, K. Kangawa and T. Sakai: Regulational effect of Ghrelin on growth-hormone secretion from perifused rat anterior pituitary cells. J. Neuroendocrinol. 14(2), 156-162 2002
  33. Sakata I., K. Nakamura, M. Yamazaki, M. Matsubara, Y. Hayashi, K. Kangawa and T. Sakai: Ghrelin-producing cells exist as two types cells, closed- and opened-type cells, in the rat gastrointestinal tract. Peptides 23(3), 531-536 2002
  34. Nakamura K., S. Kimura, A. Kawaguchi, K. Inoue and T. Sakai: Immunohistochemical analyses of thyroid-sepecific enhancer-binding protein in the fetal and adult rat hypothalami and pituitary glands. Developmental Brain Research 130(2), 159-166 2001
  35. Sakamoto S., K. Nakamura, K. Inoue and T. Sakai: Melatonin stimulates thyroid-stimulating hormone accumulation in the thyrotropes of the rat pars tuberalis. Histochemistry and Cell Biology 114, 213-218 2000
  36. Chen L., D. Maruyama, M. Sugiyama, T. Sakai, C. Mogi, M. Kato, R. Kurotani, N. Shirasawa, A. Takagi, U. Renner, Y. Kato, and K. Inoue: Cytological characterization of a pituitary folliculo-stellate like cell line, Tpit/F1, with special reference to ATP-mediated nNOS expression and NO secretion. Endocrinology 141(10), 3603-3610 2000
  37. Tsukamura H., S. Tsukahara, F. Maekawa, R. Moriyama, B. Reyes, T. Sakai, Y. Niwa, D. Foster and K. Maeda: Peripheral or Central Administration of Motilin Suppresses LH Release in Female Rats: a Novel Role for Motilin. J Neuroendocrinol. 12(5), 403-408 2000
  38. Sakai T., S. Sakamoto, K. Ijima, K. Matsubara, Y. Kato and K. Inoue: Characterization of TSH-positive cells in foetal rat pars tuberalis that fail to express Pit-1 factor and thyroid hormone b2 receptors. J. Neuroendocrinol. 11, 187-193 1999
  39. Chen L., T. Sakai, S. Sakamoto, M. Kato, and K. Inoue: Direct evidence of gonadotropin-releasing hormone (GnRH)-stimulated nitric oxide production in the LβT-2 clonal gnadotropes. Pituitary 2, 191-196 1999
  40. Goda H., T. Sakai, M. Kurosumi and K. Inoue: Prolactin-producing cells differentiate from G0/G1-arrested somatotrophs in vitro: an analysis of cell cycle phases and mammotroph differentiation. Endocrine Journal 45(6), 725-735 1998
  41. Ogawa S, Ishibashi Y, Sakamoto Y, Kitamura K, Kubo M, Sakai T, Inoue K: The glycoproteins that occur in the colloids of senescent porcine pituitary glands are clusterin and glycosylated albumin fragments. Biochem Biophys Res Commun 234, 712-18 1997
  42. Nakajima M, Shiihara Y, Shiba Y, Sano I, Sakai T, Mizumoto A, Itoh Z: Effect of 5-hydroxytryptamine on gastrointestinal motility in conscious guinea-pigs. Neurogastroenterol Motil. 9, 205-14 1997
  43. Inui A., Fujimiya M., Sakai T: Genetically engineered animals models of obesity and body weight regurlation. Current Topics in Pharmacology 3, 123-35 1997
  44. Sano I, Mizumoto A, Sakai T, Tamura T, Itoh Z: Sodium azide induces relaxation of the canine gastric body by activating a guanylate cyclase-dependent pathway. Neurogastroenterol Motil 9, 193-201 1997
  45. Mochiki E, Satoh M, Tamura T, Haga N, Suzuki H, Mizumoto A, Sakai T, Itoh Z: Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog. Gastroenterology 111, 1456-64 1996
  46. Ogawa S, Couch EF, Kubo M, Sakai T, Inoue K: Histochemical study of follicles in the senescent porcine pituitary gland. Arch Histol Cytol. 59, 467-78 1996
  47. Iesaki K, Sakai T, Satoh M, Haga N, Koyama H, Itoh Z: Distribution of enteric neural peptide YY in the dog gastrointestinal tract. Peptides 16(8), 1395-402 1995
  48. Koyama C, Matsumoto H, Sakai T, Wakabayashi K, Ito A, Couch EF, Inoue K: Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice. Endocr Pathol. 6(1), 67-75 1995
  49. Sonobe K, Sakai T, Satoh M, Haga N, Itoh Z: Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors in the vagal pathway and gallbladder in the dog. Regul Pept 60, 33-46 1995
  50. Satoh M, Sakai T, Koyama H, Shiba Y, Itoh Z: Immunocytochemical localization of motilin-containing cells in the rabbit gastrointestinal tract. Peptides 16(5), 883-87 1995
  51. Sakai T, Satoh M, Hayashi H, Fujikura K, Sano I, Koyama H, Tatemoto K, Itoh Z: Biotinyl C-terminal-extended motilin as a biologically active receptor probe. Peptides 15(2), 257-62 1994
  52. Sakai T, Satoh M, Koyama H, Iesaki K, Umahara M, Fujikura K, Itoh Z: Localization of motilin-immunopositive cells in the rat intestine by light microscopic immunocytochemistry. Peptides 15(6), 987-91 199
  53. Sakai T, Satoh M, Sonobe K, Nakajima M, Shiba Y, Itoh Z: Autoradiographic study of motilin binding sites in the rabbit gastrointestinal tract. Regul Pept. 53, 249-57 1994
  54. Satoh M, Sakai T, Sano I, Fujikura K, Koyama H, Ohshima K, Itoh Z, Omura S: EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum. J Pharmacol Exp Ther. 271(1), 574-9 1994
  55. Ohshima K, Onai T, Okada S, Umahara M, Sato M, Nakamura Y, Mori M, Kobayashi I, Sakai T: Medialbasal hypothalamic deafferentation modulates feeding response to insulin in rats. Physiol Behav. 53, 867-71 1993
  56. Sakai T, Inoue K, Kurosumi K: Light and electron microscopic immunocytochemistry of TSH-like cells occurring in the pars tuberalis of the adult male rat pituitary. Arch Histol Cytol. 55(2), 151-57 1992
  57. Inoue K, Sakai T, Hattori M: The cell-adhesive effect of basic fibroblast growth factor on pituitary cells in vitro. J Endocrinol 130, 381-86 1991
  58. Inoue K, Sakai T: Conversion of growth hormone-secreting cells into prolactin-secreting cells and its promotion by insulin and insulin-like growth factor-1 in vitro. Exp Cell Res. 195, 53-58 1991
  59. Inoue K, Hattori M, Sakai T, Inukai S, Fujimoto N, Ito A: Establishment of a series of pituitary clonal cell lines differing in morphology, hormone secretion, and response to estrogen. Endocrinology 126, 2313-20 1990
  60. Kato Y, Imai K, Sakai T, Inoue K: Simultaneous effect of gonadotropin-releasing hormone (GnRH) on the expression of two gonadotropin beta genes by passive immunization to GnRH. Mol Cell Endocrinol. 62, 2313-20 1989
  61. Sakai T, Inoue K, Hasegawa Y, Kurosumi K: Effect of passive immunization to gonadotropin-releasing hormone (GnRH) using GnRH antiserum on the mitotic activity of gonadotrophs in castrated male rats. Endocrinology 122, 2803-08 1988