2002 Fiscal Year Annual Research Report

Reg遺伝子操作マウスを用いた炎症性腸疾患治療促進機構の解析と新たな治療法の開発

Research Project

Project/Area Number	14370183
Research Institution	Shimane Medical University
Principal Investigator	木下芳一島根医科大学, 医学部, 教授 (30243306)
Keywords	Regタンパク / 腸炎 / マウス / サイトメガロウイルス / 炎症性サイトカイン / トランスジェニックマウス / ノックアウトマウス / 炎症
Research Abstract	炎症性腸疾患は極めて治療が困難で難病に指定されている。本研究では私共が消化管の強力な増殖因子であることを発見したReg蛋白を消化管に高発現させることによって炎症性腸疾患の治癒を促進させることが可能であるか否かを検討している。本年度はReg蛋白を全身臓器で高発現するサイトメガロウイルスプロモーターを有するRegトランスジェニックマウス、Reg蛋白を消化管上皮でのみ高発現するトレフォイルペプチドプロモーターを有するRegトランスジェニックマウス、そしてReg遺伝子を欠損するRegノックアウトマウスの3種のモデル動物を用意した。これらのマウスに飲水中にDSSを混入することによりDSS colitisを、TNBSを注腸することによってTNBS colitisを作製し、炎症性腸疾患のモデルとした。現在、これらのDSS colitis、TNBS colitisの形態学的な粘膜欠損部位の広さの測定、組織学的な検討による炎症性細胞の浸潤の程度の計測、PCNA染色による腸管上皮細胞の増殖度について検討を行っている。プレリミナリーな成績では、Regを高発現するトランスジェニックマウスでは血中Reg蛋白の高値を示すサイトメガロプロモーターを有するものでも、血中Reg蛋白の高値を伴わないものでもcolitisの誘発によって粘膜上皮の著明な増殖亢進が観察された。一方、RegのノックアウトマウスではColitisを作製しても粘膜上皮細胞の増殖の亢進はコントロールマウスに比較して軽度であった。一方、炎症のマーカーと考えられる白血球系細胞の浸潤、炎症性サイトカインの発現は各マウスにおいて著明な差異は認められなかった。この成績は、Reg蛋白が消化管上皮の増殖をin vivoで促進することを確認するとともに、炎症性腸疾患の治療薬としてのRegの有効性を示す、画期的な成績と考えられる。平成15、16年度はこのプレリミナリーな成績を確認するとともにマウスが成長した後にRegの発現量を調整できる遺伝子操作マウスを用いて検討を行っていく。

Research Products

(31 results)

All Other

All Publications (31 results)

[Publications] Okuyama T, et al.: "A novel doudenal elevated lesion mimicking intraluminal doudenal"Gastrointestinal Endoscopy. 55. 750-752 (2002)
[Publications] Hashimoto T, et al.: "Safety and efficacy of glucagon as a premedication for upper"Alimentary Pharmacology and Therapeutics. 16. 111-118 (2002)
[Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"J. Lab. Clin. Med. 139. 101-108 (2002)
[Publications] Adachi K, et al.: "Nizatidine and cisapride enhance salivary secretion in human"Alimentary Pharmacoligy and Therapeutics. 16. 297-301 (2002)
[Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. 7. 86-90 (2002)
[Publications] Kawashima K, et al.: "Locolization of calcitonin gene-related peptide receptors in rat"Peptides. 23. 955-966 (2002)
[Publications] Kijima I, et al.: "The distribution of endocrin cells in surgically resected"J Gastroenterology. 37. 396-397 (2002)
[Publications] Kaji T, et al.: "Adherence of Helicobacter pylori to gastric epithelial"J. Lab. Cli. Med. 139. 244-250 (2002)
[Publications] Kazumori H, et al.: "Time course changes of ECL cell markers in acetic acid-induced"Alimentary pharmacology and Therapeutics. 16. 10-19 (2002)
[Publications] Sato H, et al.: "Primary hyperparathyroidism with duodenal ulcer and"Internal Medicine. 41. 377-380 (2002)
[Publications] Yuki M, et al.: "Is computerized bowel sound auscultation system useful for the"Am j. Gastroenterol. 97. 1846-1848 (2002)
[Publications] Rumi Mak, et al.: "Growth inhibition of esophageal squamous carcinoma cells"J. Lab. Clin med. 140. 17-26 (2002)
[Publications] Endo H, et al.: "Fine reconstruction of the pancreatic ductular system at the"Histol Histopathol. 17. 107-112 (2002)
[Publications] Adachi K, et al.: "Comparative evaluation of urine-based and other minimally invasive"J. Gastroenterology. 37. 703-708 (2002)
[Publications] Sato H, et al.: "Successful endoscopic injection sclerotherapy for duodenal"J. Gastroenterology. 37. 143-144 (2002)
[Publications] Adachi K, et al.: "Nocturnal gastric acid breakthrough and"Gastrointestinal Function Regulation and Disturbances. 19. 47-56 (2002)
[Publications] Kawamura A, et al.: "Helicobacter pylori-independent effect of hyperglycemia on gastric"Am. J. Gastroenterol. 97. 2479-2480 (2002)
[Publications] Kinoshita Y, et al.: "Efficacy of rabeprazole in patients with reflux"Current Therapeutic Res. 63. 810-820 (2002)
[Publications] Okuyama T, et al.: "Activation of prostaglandin E2 receptor"J. Lab. Clin. Med. 140. 92-102 (2002)
[Publications] Okuyama T, et al.: "Angiolipoma of the colon diagnosed after endoscopic"Gastrointest Endosc. 55. 748-750 (2002)
[Publications] Matsushima Y, et al.: "Immunological and molecular analysis of B lymphocytes"J. Gastroenterol. 37. 428-433 (2002)
[Publications] Yoshino N, et al.: "Helicobacter pylori infection does not affect the serum"Am J Gastroenterol. 97. 2979-2928 (2002)
[Publications] Hamamoto N, et al.: "A new water instillation method for painless total"Gastrointest Endosc. 56. 825-828 (2002)
[Publications] Katsube T, et al.: "Comparison of two kinds of special test meals"Shimane J. Med. 20. 5-8 (2002)
[Publications] Ortaga-Cava CF, et al.: "Hepatocyte growth factor expression in dextran sodium"Dig. Dis. Sci. 47. 2275-2285 (2002)
[Publications] Kadowaki Y, et al.: "Reg protein is overexpressed in gastric cancer cells"FEBS Lett.. 530. 59-64 (2002)
[Publications] Hamamoto N, et al.: "Morphological changes in the rat exocrine pancreas after"Histol. Histopathol. 17. 1033-1041 (2002)
[Publications] Adachi K, et al.: "Influence of lansoprazole, famotidine, roxatidine"J. Gastroenterol. Hepatol. 18. 168-171 (2003)
[Publications] Sato H, et al.: "Lafutidine pretreatment causes increase in serum"J. Lab. Clin. Med. 141. 102-105 (2003)
[Publications] Hamamoto S, et al.: "9-cis retinoic acid enhances the anti-viral effect of interferon"J. Lab. Clin. Med. 141. 58-66 (2003)
[Publications] Fujishiro H, et al.: "Analysis of urgent colonoscopy for acute lower intestinal"Digestive Endoscopy. 15. 117-120 (2003)

2002 Fiscal Year Annual Research Report

Reg遺伝子操作マウスを用いた炎症性腸疾患治療促進機構の解析と新たな治療法の開発

Principal Investigator

木下 芳一 島根医科大学, 医学部, 教授 (30243306)

Research Products

[Publications] Okuyama T, et al.: "A novel doudenal elevated lesion mimicking intraluminal doudenal"Gastrointestinal Endoscopy. 55. 750-752 (2002)

[Publications] Hashimoto T, et al.: "Safety and efficacy of glucagon as a premedication for upper"Alimentary Pharmacology and Therapeutics. 16. 111-118 (2002)

[Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"J. Lab. Clin. Med. 139. 101-108 (2002)

[Publications] Adachi K, et al.: "Nizatidine and cisapride enhance salivary secretion in human"Alimentary Pharmacoligy and Therapeutics. 16. 297-301 (2002)

[Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. 7. 86-90 (2002)

[Publications] Kawashima K, et al.: "Locolization of calcitonin gene-related peptide receptors in rat"Peptides. 23. 955-966 (2002)

[Publications] Kijima I, et al.: "The distribution of endocrin cells in surgically resected"J Gastroenterology. 37. 396-397 (2002)

[Publications] Kaji T, et al.: "Adherence of Helicobacter pylori to gastric epithelial"J. Lab. Cli. Med. 139. 244-250 (2002)

[Publications] Kazumori H, et al.: "Time course changes of ECL cell markers in acetic acid-induced"Alimentary pharmacology and Therapeutics. 16. 10-19 (2002)

[Publications] Sato H, et al.: "Primary hyperparathyroidism with duodenal ulcer and"Internal Medicine. 41. 377-380 (2002)

[Publications] Yuki M, et al.: "Is computerized bowel sound auscultation system useful for the"Am j. Gastroenterol. 97. 1846-1848 (2002)

[Publications] Rumi Mak, et al.: "Growth inhibition of esophageal squamous carcinoma cells"J. Lab. Clin med. 140. 17-26 (2002)

[Publications] Endo H, et al.: "Fine reconstruction of the pancreatic ductular system at the"Histol Histopathol. 17. 107-112 (2002)

[Publications] Adachi K, et al.: "Comparative evaluation of urine-based and other minimally invasive"J. Gastroenterology. 37. 703-708 (2002)

[Publications] Sato H, et al.: "Successful endoscopic injection sclerotherapy for duodenal"J. Gastroenterology. 37. 143-144 (2002)

[Publications] Adachi K, et al.: "Nocturnal gastric acid breakthrough and"Gastrointestinal Function Regulation and Disturbances. 19. 47-56 (2002)

[Publications] Kawamura A, et al.: "Helicobacter pylori-independent effect of hyperglycemia on gastric"Am. J. Gastroenterol. 97. 2479-2480 (2002)

[Publications] Kinoshita Y, et al.: "Efficacy of rabeprazole in patients with reflux"Current Therapeutic Res. 63. 810-820 (2002)

[Publications] Okuyama T, et al.: "Activation of prostaglandin E2 receptor"J. Lab. Clin. Med. 140. 92-102 (2002)

[Publications] Okuyama T, et al.: "Angiolipoma of the colon diagnosed after endoscopic"Gastrointest Endosc. 55. 748-750 (2002)

[Publications] Matsushima Y, et al.: "Immunological and molecular analysis of B lymphocytes"J. Gastroenterol. 37. 428-433 (2002)

[Publications] Yoshino N, et al.: "Helicobacter pylori infection does not affect the serum"Am J Gastroenterol. 97. 2979-2928 (2002)

[Publications] Hamamoto N, et al.: "A new water instillation method for painless total"Gastrointest Endosc. 56. 825-828 (2002)

[Publications] Katsube T, et al.: "Comparison of two kinds of special test meals"Shimane J. Med. 20. 5-8 (2002)

[Publications] Ortaga-Cava CF, et al.: "Hepatocyte growth factor expression in dextran sodium"Dig. Dis. Sci. 47. 2275-2285 (2002)

[Publications] Kadowaki Y, et al.: "Reg protein is overexpressed in gastric cancer cells"FEBS Lett.. 530. 59-64 (2002)

[Publications] Hamamoto N, et al.: "Morphological changes in the rat exocrine pancreas after"Histol. Histopathol. 17. 1033-1041 (2002)

[Publications] Adachi K, et al.: "Influence of lansoprazole, famotidine, roxatidine"J. Gastroenterol. Hepatol. 18. 168-171 (2003)

[Publications] Sato H, et al.: "Lafutidine pretreatment causes increase in serum"J. Lab. Clin. Med. 141. 102-105 (2003)

[Publications] Hamamoto S, et al.: "9-cis retinoic acid enhances the anti-viral effect of interferon"J. Lab. Clin. Med. 141. 58-66 (2003)

[Publications] Fujishiro H, et al.: "Analysis of urgent colonoscopy for acute lower intestinal"Digestive Endoscopy. 15. 117-120 (2003)

木下芳一島根医科大学, 医学部, 教授 (30243306)