The pathoetiology of destruction and regeneration in salivary gland of Sjogren's syndrome

• Project/Area Number: 22591096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Nara Medical University
• Principal Investigator: FUJIMOTO Takashi 奈良県立医科大学, 医学部, 准教授 (60264850)
• Co-Investigator(Kenkyū-buntansha): TAKASWA Shin 奈良県立医科大学, 医学部, 教授 (50187944) ; KASAI Takahiko 奈良県立医科大学, 医学部, 助教 (50224374)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 免疫学 / シェーグレン症候群 / REG

Research Abstract

Sjogren’s syndrome (SS) is a chronic autoimmune disease, characterized by inflammation of salivary and lacrimal glands, leading to dry mouth and dry eye. The regenerating gene (Reg) was originally isolated as a gene specifically overexpressed in regenerating pancreatic islets. In this study, we examined the expression of REG genes in the salivary glands (SG) and anti-REG autoantibodies in SS. These data strongly suggest that autoimmunity to REG may play a role in the degeneration of SG ductal epithelial cells in SS.

Research Products

• [Journal Article] Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjogren's syndrome (2013)
  • Author(s): Yoshimoto K, Fujimoto T, Itaya-HironakaA, Miyaoka T, Sakuramoto-Tsuchida S, Yamauchi A, Takeda M, Kasai T, Nakagawara K, Nonomura A, Takasawa S
  • Journal Title: Clin Exp Immunol
  • Peer Reviewed
• [Journal Article] The advantages of three-dimensional culture in a collagen hydrogel for stem cell differentiation (2013)
  • Author(s): Naito H, Yoshimura M, Mizuno T, Takasawa S, Tojo T, Taniguchi S
  • Journal Title: J Biomed Mater Res A
  • Peer Reviewed
• [Journal Article] Reg3G gene expression in regenerating skeletal muscle and corresponding nerve. (2013)
  • Author(s): Klasan GS, Ivanac D, Erzen DJ, Picard A, Takasawa S, Peharec S, Arbanas J, Girotto D, Jerkovic R
  • Journal Title: Muscle Nerve
  • Peer Reviewed
• [Journal Article] Biomarkers for diagnosis and monitoring of celiac disease (2013)
  • Author(s): Vives-Pi M, Takasawa S, Pujol-Autonell I, Planas R, Cabre E, Ojanguren I, Montraveta M, Santos AL, Ruiz-Ortiz E
  • Journal Title: J Clin Gastroenterol Volume: 47 Pages: 308-13
  • Peer Reviewed
• [Journal Article] Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjogren’s syndrome (2013)
  • Author(s): Yoshimoto K, Fujimoto T, Itaya-HironakaA, Miyaoka T, Sakuramoto-Tsuchida S, Yamauchi A, Takeda M, Kasai T, Nakagawara K, Nonomura A, Takasawa S
  • Journal Title: Clin Exp Immunol Volume: -
  • Peer Reviewed
• [Journal Article] The advantages of three-dimensional culture in a collagen hydrogel for stem cell differentiation. (2013)
  • Author(s): Naito H, Yoshimura M, Mizuno T, Takasawa S, Tojo T, Taniguchi S.
  • Journal Title: J Biomed Mater Res A Volume: Epub ahead of print Issue: 10 Pages: 2838-2845
  • DOI: 10.1002/jbm.a.34578
  • Peer Reviewed
• [Journal Article] Reg3G gene expression in regenerating skeletal muscle and corresponding nerve (2013)
  • Author(s): Klasan GS, Ivanac D, Erzen DJ, Picard A, Takasawa S, Peharec S, Arbanas J, Girotto D, Jerkovic R.
  • Journal Title: Muscle Nerve Volume: Epub ahead of print Issue: 1 Pages: 61-68
  • DOI: 10.1002/mus.23877
  • Peer Reviewed
• [Journal Article] Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate (2012)
  • Author(s): Ikeda T, Takasawa S, Noguchi N, Nata K, Yamauchi A, Takahashi I, Yoshikawa T, Sugawara A, Yonekura H, Okamoto H
  • Journal Title: Mol Cell Biochem Volume: 366 Pages: 69-80
  • Peer Reviewed
• [Journal Article] Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38 (2012)
  • Author(s): Ota H, Tamaki S, Itaya-Hironaka A, Yamauchi A, Sakuramoto-Tsuchida S, Morioka T, Takasawa S, Kimura H
  • Journal Title: Life Sci Volume: 90 Pages: 206-11
  • Peer Reviewed
• [Journal Article] Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate (2012)
  • Author(s): Ikeda T, Takasawa S, Noguchi N, Nata K, Yamauchi A, Takahashi I, Yoshikawa T, Sugawara A, Yonekura H, Okamoto H.
  • Journal Title: Mol Cell Biochem Volume: 366 Issue: 1-2 Pages: 69-80
  • DOI: 10.1007/s11010-012-1284-0
  • Peer Reviewed
• [Journal Article] Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38 (2012)
  • Author(s): Ota H, Takasawa S
  • Journal Title: Life Sci Volume: 90 Issue: 5-6 Pages: 206-211
  • DOI: 10.1016/j.lfs.2011.11.011
  • Peer Reviewed
• [Journal Article] Deletion of platelet-derived growth factor receptor-β improves diabetic nephropathy in Ca^2+/calmodulin-dependent protein kinase Iiα (Thr286Asp) transgenic mice (2011)
  • Author(s): Suzuki H, Usui I, Kato I, Oya T, Kanatani Y, Yamazaki Y, Fujisaka S, Senda S, Ishii Y, Urakaze M, Mahmood A, Takasawa S, Okamoto H, Kobayashi M, Tobe K, Sasahara M
  • Journal Title: Diabetologia. Volume: 54 Pages: 2953-62
  • Peer Reviewed
• [Journal Article] Septic shock is associated with receptor for advanced glycation end products ligation of LPS (2011)
  • Author(s): Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T, Asano M, Takasawa S, Okamoto H, Shimura S, Karasawa T, Yonekura H, Yamamoto H
  • Journal Title: J Immunol. Volume: 186 Pages: 3248-3257
  • Peer Reviewed
• [Journal Article] Expression profile of the REG gene family in colorectal carcinoma (2011)
  • Author(s): Zheng HC, Sugawara A, Okamoto H, Takasawa S, Takahashi H, Masuda S, Takano Y
  • Journal Title: J Histochem Cytochem Volume: 59 Pages: 106-15
  • Peer Reviewed
• [Journal Article] The effect of mesenchymal stem cell osteoblastic differentiation on the mechanical properties of engineered bone-like tissue (2011)
  • Author(s): Naito H, Dohi Y, Zimmermann WH, Tojo T, Takasawa S, Eschenhagen T, Taniguchi S
  • Journal Title: Tissue Eng Part A Volume: 17 Pages: 2321-2329
  • Peer Reviewed
• [Journal Article] Deletion of platelet-derived growth factor receptor-β improves diabetic nephropathy in Ca^<2+>/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice (2011)
  • Author(s): Suzuki H.
  • Journal Title: Diabetologia Volume: 54 Issue: 11 Pages: 2953-2962
  • DOI: 10.1007/s00125-011-2270-x
  • Peer Reviewed
• [Journal Article] Expression profile of the REG gene family in colorectal carcinoma (2011)
  • Author(s): Zheng HC, Takasawa S
  • Journal Title: J Histochem Cytochem Volume: 59 Issue: 1 Pages: 106-115
  • DOI: 10.1369/jhc.2010.956961
  • Peer Reviewed
• [Journal Article] Septic shock is associated with receptor for advanced glycation end products ligation of LPS (2011)
  • Author(s): Yamamoto Y, Takasawa S
  • Journal Title: J Immunol Volume: 186 Issue: 5 Pages: 3248-3257
  • DOI: 10.4049/jimmunol.1002253
  • Peer Reviewed
• [Journal Article] Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosus (2010)
  • Author(s): Yamaguchi H, Fujimoto T, Nakamura S, Ohmura K, Mimori T, Matsuda F, Nagata S.
  • Journal Title: Eur J Immunol Volume: 40 Pages: 1778-1785
  • Peer Reviewed
• [Journal Article] In vivo evidence for the role of Reg I in gastric regeneration: Transgenic overexpression of Reg accelerates the healing of experimental gastric ulcers (2010)
  • Author(s): Fukuhara H, Kadowaki Y, Ose I, Ishihara, S, Takasawa S, Kinoshita Y
  • Journal Title: Lab Invest Volume: 190 Pages: 555-565
  • Peer Reviewed
• [Journal Article] Exacerbation of indomethacin-induced small intestinal injuries in Reg I-knockout mice (2010)
  • Author(s): Imaoka H, Ishihara S, Kadowaki Y, Aziz Md M, Rahman F R, Ose T, Fukuhara H, Takasawa S. Kinoshita, Y
  • Journal Title: Am J physiol Gastrointesitnal Liver Physiol Volume: 299
  • Peer Reviewed
• [Journal Article] Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells (2010)
  • Author(s): Usami S, Motoyama S, Koyota S, Wang J, Hayashi-Shibuya K, Maruyama K, Takahashi N, Saito H, Minamiya Y, Takasawa S, Ogawa J I, Sugiyama T
  • Journal Title: Biochem Biophys Res Commun Volume: 392 Pages: 4-8
  • Peer Reviewed
• [Journal Article] Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosus (2010)
  • Author(s): Yamaguchi H, Fujimoto T
  • Journal Title: Eur.J.Immunol. Volume: VOL.40 Pages: 1778-1785
  • Peer Reviewed
• [Journal Article] A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene (2010)
  • Author(s): Takasawa S
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: VOL.397 Pages: 140-145
  • Peer Reviewed
• [Journal Article] In vivo evidence for the role of Reg I in gastric regeneration : Transgenic overexpression of Reg accelerates the healing of experimental gastric ulcers. (2010)
  • Author(s): Fukuhara H, Takasawa S
  • Journal Title: Lab.Invest. Volume: VOL.190 Pages: 555-565
  • Peer Reviewed
• [Journal Article] Exacerbation of indomethacin-induced small intestinal injuries in Reg I-knockout mice. (2010)
  • Author(s): Imaoka, H., Takasawa, S
  • Journal Title: Am.J.physiol.Gastrointesitnal Liver Physiol. Volume: VOL.299
  • Peer Reviewed
• [Journal Article] Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells. (2010)
  • Author(s): Usami S, Takasawa S
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: VOL.392 Pages: 4-8
  • Peer Reviewed
• [Journal Article] A study on the effect of autoanitibodies to human REG (Regenerating gene) family proteins in type 1 and type2 diabetes. (2010)
  • Author(s): Shervani N J, Takasawa S
  • Journal Title: 糖尿病 Volume: VOL.53
• [Journal Article] Transcriptinal analysis of human REG family genes in pancreatic β-cells. (2010)
  • Author(s): Yamauchi A, Takasawa S
  • Journal Title: Diabetes Volume: VOL.59
• [Presentation] NON-STEROIDAL ANTI-INFLAMMATORY DRUGS HAVE AN INDEPENDENT EFFECT ON SYNOVIAL VASCULARITY ASSESSED BY MUSCULOSKELETAL ULTRASOUND IN RHEUMATOID ARTHRITIS (2013)
  • Author(s): Fujimura T, Fujimoto T
  • Organizer: Annual European Congress of Rheumatology (EULAR) 2013
  • Place of Presentation: Madrid (Spain)
  • Year and Date: 2013-06-12
• [Presentation] INDUCTION OF REG IΑ, A NEW AUTO-ANTIGEN IN SJOGREN'S SYNDROME PATIENTS, IN SALIVARY DUCT EPITHELIAL CELLS BY INTERLEUKIN-6 AND -11 (2013)
  • Author(s): Fujimura T, Takasawa S, Fujimoto T
  • Organizer: Annual European Congress of Rheumatology (EULAR) 2013
  • Place of Presentation: Madrid (Spain)
  • Year and Date: 2013-06-12
• [Presentation] INDUCTION OF REG IΑ, A NEW AUTO-ANTIGEN IN SJOGREN’S SYNDROME PATIENTS, IN SALIVARY DUCT EPITHELIAL CELLS BY INTERLEUKIN-6 AND -11 (2013)
  • Author(s): Fujimura T, Itaya-Hironaka A, Miyaoka T, Yoshimoto K, Sakuramoto-Tsuchida S, Yamauchi A, Tsujinaka H, Takasawa S, Fujimoto T
  • Organizer: Annual European Congress of Rheumatology (EULAR) 2013
  • Place of Presentation: Madrid (Spain)
• [Presentation] NON-STEROIDAL ANTI-INFLAMMATORY DRUGS HAVE AN INDEPENDENT EFFECT ON SYNOVIAL VASCULARITY ASSESSED BY MUSCULOSKELETAL ULTRASOUND IN RHEUMATOID ARTHRITIS (2013)
  • Author(s): Fujimura T, Fujimoto T, Hara R, Shimmyo N, Kobata Y, Kido A, Akai Y, Tanaka Y
  • Organizer: Annual European Congress of Rheumatology (EULAR) 2013
  • Place of Presentation: Madrid (Spain)
• [Presentation] ゴリムマブが効果不十分な活動性関節リウマチ患者に対するミゾリビンパルス併用療法の有効性の検討 (2013)
  • Author(s): 藤村貴則、藤本隆、原良太、新名直樹、城戸顕、小畠康宣、赤井靖宏、田中康仁
  • Organizer: 第57日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都市（京都府）
• [Presentation] The JAK/STAT signaling is essential for human REG Iα transcription in pancreatic β cells (2012)
  • Author(s): Yamauchi, A. Takasawa, S
  • Organizer: The 9th IDF-WPR Congress/4th AASD Scientific Meeting
  • Place of Presentation: Kyoto (Japan)
  • Year and Date: 2012-11-24
• [Presentation] Pancreatic β cell proliferation by intermittent hypoxia via up-regulation of Reg family genes (2012)
  • Author(s): Takasawa S
  • Organizer: The 48th EASD Meeting
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 2012-10-01
• [Presentation] 原発性シェーグレン症候群の関節炎-超音波検査による検討- (2012)
  • Author(s): 藤村 貴則、藤本 隆
  • Organizer: 第56日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] The JAK/STAT signaling is essential for human REG Iα transcription in pancreatic β cells. (2012)
  • Author(s): Yamauchi, A., Itaya-Hironaka, A., Sakuramoto-Tsuchida, S., Yoshimoto, K., Miyaoka, T., Fujimura, T., Tsujinaka, H., Tsuchida, C., Ota, H., Takasawa, S.
  • Organizer: The 9th IDF-WPR Congress/4th AASD Scientific Meeting
  • Place of Presentation: 京都市（京都府）
• [Presentation] Intermittent hypoxia stimulates β cell proliferation via up-regulation of Reg family genes (2012)
  • Author(s): Takasawa, S., Ota, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Fujimura, T., Tsujinaka, H., Yoshimoto, K., Tsuchida, C., Tamaki, S., Kimura, H.
  • Organizer: The 9th IDF-WPR Congress/4th AASD Scientific Meeting
  • Place of Presentation: 京都市（京都府）
• [Presentation] 膵β細胞におけるヒトREG (Regenerating gene)ファミリー遺伝子のIL-6/デキサメサゾンによる転写誘導とその機構 (2012)
  • Author(s): 山内晶世、広中安佐子、土田澄代、吉本清巳、宮岡朋子、藤村貴則、辻中大生、土田親次、太田浩世、高沢 伸
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市（福岡県）
• [Presentation] 原発性シェーグレン症候群の関節炎-超音波検査による検討- (2012)
  • Author(s): 藤村 貴則、藤本 隆、原 良太、小畠 康宣、新名 直樹、赤井 靖宏、田中 康仁
  • Organizer: 第56日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京都
• [Presentation] Involvement of autoimmunity to REG in patients with primary Sjogren's syndrome (2011)
  • Author(s): Fujimoto T, Yoshimoto K, Takasawa S
  • Organizer: The 11th International Symposium on Sjogren's Sydrome
  • Place of Presentation: Athens(Greece)
  • Year and Date: 2011-09-29
• [Presentation] シェーグレン症候群の唾液腺障害における REGの関与について (2011)
  • Author(s): 吉本清巳、藤本 隆
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-07-19
• [Presentation] シェーグレン症候群の唾液腺障害におけるREGの関与について (2011)
  • Author(s): 吉本清巳、藤本隆
  • Organizer: 日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2011-07-19
• [Presentation] REG family genes expression in lung cancer (2011)
  • Author(s): Naito H, Takasawa S
  • Organizer: International Association for the Study of Lung Cancer
  • Place of Presentation: Amsterdam (Netherlands)
  • Year and Date: 2011-07-03
• [Presentation] IL‐6/ Dexamethasone activated the human REG Ia gene transcription in pancreaticβ‐cells via the JAK/STAT signaling pathway (2011)
  • Author(s): Yamauchi A, Takasawa S
  • Organizer: The 71st American Diabetes Association Scientific Sessions
  • Place of Presentation: San Diego(USA)
  • Year and Date: 2011-06-24
• [Presentation] Autoimmunity to REG, in patients with primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto K, Fujimoto T, Takasawa S
  • Organizer: Annual European Congress of Rheumatology EULAR 2011
  • Place of Presentation: London(UK)
  • Year and Date: 2011-05-27
• [Presentation] Autoimmunity to REG, in patients with primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto K, Fujimoto T, Takasawa S
  • Organizer: Annual European Congress of Rheumatology EULAE 2011
  • Place of Presentation: London(UK)
  • Year and Date: 2011-05-27
• [Presentation] Therapeutic effect of recombinant DNaseII on the arthritis caused by DNA escaped from degradation (2011)
  • Author(s): Fujimoto T, Kawane K, Nagata S
  • Organizer: The13th international TNF conference
  • Place of Presentation: Hyogo
  • Year and Date: 2011-05-17
• [Presentation] Therapeutic effect of recombinant DNaseII on the arthritis caused by DNA escaped from degradation (2011)
  • Author(s): Fujimoto T, Kawane K, Nagata S
  • Organizer: The13th international TNF conference
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫県)
  • Year and Date: 2011-05-17
• [Presentation] シェーグレン症候群の唾液腺障害機序における REG(regenerating gene product)の発現と自己抗体の関係 (2010)
  • Author(s): 吉本清巳、藤本 隆、高澤 伸
  • Organizer: 第19回日本シェーグレン症候群学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-09
• [Presentation] シェーグレン症候群の唾液腺障害機序におけるREG(regenerating gene product)の発現と自己抗体の関係 (2010)
  • Author(s): 吉本清巳、藤本隆、高澤伸
  • Organizer: 第19回日本シェーグレン症候群学会
  • Place of Presentation: ホテルオークラ東京ベイ(千葉県)
  • Year and Date: 2010-09-09
• [Presentation] Autoantibodies to REG, a regeneration factor, in patients with primary Sjogren syndrome (2010)
  • Author(s): Yoshimoto K, Fujimoto T, Takasawa S
  • Organizer: 14th Asia Pacific League of Associations for Rheumatology (APLAR) Congress
  • Place of Presentation: Hong Kong(China)
  • Year and Date: 2010-07-12
• [Presentation] Autoantibodies to REG, a regeneration factor, in patients with primary Sjogren syndrome (2010)
  • Author(s): Yoshimoto K, Fujimoto T, Takasawa S
  • Organizer: 14th Asia Pacific League of Associations for Rheumatology (APLAR) Congress
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2010-07-12
• [Presentation] 原発性シェーグレン症候群患者における REG に対する自己抗体について (2010)
  • Author(s): 吉本清巳、藤本 隆、高澤 伸
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-04-22
• [Presentation] 原発性シェーグレン症候群患者におけるREGに対する自己抗体について (2010)
  • Author(s): 吉本清巳、藤本隆、高澤伸
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
  • Year and Date: 2010-04-22
• [Presentation] 膵β細胞におけるヒトREG(Regenerating gene)ファミリー遺伝子のIL-6/デキサメサゾンによる転写誘導 (2010)
  • Author(s): 山内晶世、高澤伸
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会・合同大会
  • Place of Presentation: 神戸国際会議場(兵庫県)