Study for the pathogenesis of autoimmune diseases using sphingomyeline knock out mouse

2013 Fiscal Year Final Research Report

• Project/Area Number: 22249041
• Research Category: Grant-in-Aid for Scientific Research (A)
• 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: Kanazawa Medical University
• Principal Investigator: UMEHARA Hisanori 金沢医科大学, 医学部, 教授 (70247881)
• Co-Investigator(Kenkyū-buntansha): OKAZAKI Kazuichi 関西医科大学, 医学部, 教授 (70145126) ; OKAZAKI Toshiro 金沢医科大学, 医学部, 教授 (40233308) ; WATANABE Ken 独立行政法人国立長寿医療研究センター, 運動器疾患研究部, 研究室リーダー (10342966)
• Co-Investigator(Renkei-kenkyūsha): KAWANAMI Takafumi 金沢医科大学, 医学部, 講師 (20350762) ; FUJITA Yoshimasa 金沢医科大学, 医学部, 講師 (70450880)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Keywords: スフィンゴミエリン / リピッドラフト / ノックアウトマウス / 自己免疫性疾患 / 関節リウマチ

Research Abstract

We analyzed the pathogenesis of autoimmune diseases using sphingomyelin synthase 1 knockout (SMS1-KO) mouse. In vivo study showed that T cell function was impaired and cytokine production was decreased. By concanavalin A-induced hepatitis model, SMS1-KO mouse showed the amelioration of hepatitis. In addition, using collagen-induced arthritis model, we confirmed the amelioration of arthritis in SMS1-KO mouse. These results indicate that sphingomyelin has important roles in the pathogenesis of autoimmune diseases such as autoimmune hepatitis and rheumatoid arthritis through impaired functions of lipid rafts.

Research Products

• [Journal Article] Long-term Heat Exposure Prevents Hypoxia-Induced Apoptosis in Mouse Fibroblast Cells (2014)
  • Author(s): Sugimoto N, Shido O, Matsuzaki K, Katakura M, Hitomi Y, Tanaka M, Sawaki T, Fujita Y, Kawanami T, Masaki Y, Okazaki T, Nakamura H, Koizumi S, Yachie A and Umehara H
  • Journal Title: Cell biochemistry and biophysics Volume: (in press)
  • DOI: 10.1007/s12013-014-9912-9
  • Peer Reviewed
• [Journal Article] Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice (2014)
  • Author(s): Fujita Y, Fujii T, Mimori T, Sato T, Nakamura T, Iwao H, Nakajima A, Miki M, Sakai T, Kawanami T, Tanaka M, Masaki Y, Fukushima T, Okazaki T and Umehara H
  • Journal Title: Journal of immunology Volume: 192 Pages: 979-984
  • DOI: 10.4049/jimmunol.1301685
  • Peer Reviewed
• [Journal Article] Upregulation of aquaporin expression in the salivary glands of heat-acclimated rats (2013)
  • Author(s): Sugimoto N, Matsuzaki K, Ishibashi H, Tanaka M, Sawaki T, Fujita Y, Kawanami T, Masaki Y, Okazaki T, Sekine J, Koizumi S, Yachie A, Umehara H and Shido O
  • Journal Title: Scientific Reports Volume: 3 Pages: 1763
  • DOI: 10.1038/srep01763
  • Peer Reviewed
• [Journal Article] Possible Mechanisms of Lymphoma Development in Sjogren's Syndrome (2013)
  • Author(s): Dong L, Chen Y, Masaki Y, Okazaki T and Umehara H
  • Journal Title: Current Immunology Reviews Volume: 9 Pages: 13-22
  • DOI: 10.2174/1573395511309010003
  • Peer Reviewed
• [Journal Article] The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis (2013)
  • Author(s): Chen Y, Sun W, Gao R, Su Y, Umehara H, Dong L and Gong F
  • Journal Title: Rheumatology (Oxford, England) Volume: 52 Pages: 1739-1747
  • DOI: 10.1093/rheumatology/ket134
  • Peer Reviewed
• [Journal Article] Regulation of autophagy and its associated cell death by "sphingolipid rheostat": reciprocal role of ceramide and sphingosine 1-phosphate in the mammalian target of rapamycin pathway (2012)
  • Author(s): Taniguchi M, Kitatani K, Kondo T, Hashimoto-Nishimura M, Asano S, Hayashi A, Mitsutake S, Igarashi Y, Umehara H, Takeya H, Kigawa J and Okazaki T
  • Journal Title: The Journal of biological chemistry Volume: 287 Pages: 39898-39910
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23035115
  • Peer Reviewed
• [Journal Article] Cellular heat acclimation regulates cell growth, cell morphology, mitogen-activated protein kinase activation, and expression of aquaporins in mouse fibroblast cells (2012)
  • Author(s): Sugimoto N, Shido O, Matsuzaki K, Ohno-Shosaku T, Hitomi Y, Tanaka M, Sawaki T, Fujita Y, Kawanami T, Masaki Y, Okazaki T, Nakamura H, Koizumi S, Yachie A and Umehara H
  • Journal Title: Cell Physiol Biochem. Volume: 30 Pages: 450-457
  • DOI: 10.1159/000339038
  • Peer Reviewed
• [Journal Article] Loss of HITS (FAM107B) expression in cancers of multiple organs : tissue microarray analysis (2012)
  • Author(s): Nakajima H, Koizumi K, Tanaka T, Ishigaki Y, Yoshitake Y, Yonekura H, Sakuma T, Fukushima T, Umehara H, Ueno S, Minamoto T and Motoo Y
  • Journal Title: International journal of oncology Volume: 41 Pages: 1347-1357
  • DOI: 10.3892/ijo.2012.1550
  • Peer Reviewed
• [Journal Article] Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation (2012)
  • Author(s): Nakajima H, Ishigaki Y, Xia QS, Ikeda T, Yoshitake Y, Yonekura H, Nojima T, Tanaka T, Umehara H, Tomosugi N, Takata T, Shimasaki T, Nakaya N, Sato I, Kawakami K, Koizumi K, Minamoto T and Motoo Y
  • Journal Title: International journal of oncology Volume: 37 Pages: 583-593
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20664927
  • Peer Reviewed
• [Journal Article] Follistatin-related protein/follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor 4 (2012)
  • Author(s): Murakami K, Tanaka M, Usui T, Kawabata D, Shiomi A, Iguchi-Hashimoto M, Shimizu M, Yukawa N, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Umehara H and Mimori T
  • Journal Title: FEBS Lett. Volume: 586 Pages: 319-324
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22265692
  • Peer Reviewed
• [Journal Article] Skewed production of IL-6 and TGFbeta by cultured salivary gland epithelial cells from patients with Sjogren's syndrome (2012)
  • Author(s): Kawanami T, Sawaki T, Sakai T, Miki M, Iwao H, Nakajima A, Nakamura T, Sato T, Fujita Y, Tanaka M, Masaki Y, Fukushima T, Hirose Y, Taniguchi M, Sugimoto N, Okazaki T and Umehara H
  • Journal Title: PLoS One Volume: 7 Pages: e45689
  • DOI: 10.1371/journal.pone.0045689
  • Peer Reviewed
• [Journal Article] Prevention of fasting-mediated bone marrow atrophy by leptin administration (2012)
  • Author(s): Fujita Y, Yanagida H, Mimori T, Jin ZX, Sakai T, Kawanami T, Sawaki T, Masaki Y, Fukushima T, Okazaki T and Umehara H
  • Journal Title: Cellular immunology Volume: 273 Pages: 52-58
  • DOI: 10.1016/j.cellimm.2011.11.007
  • Peer Reviewed
• [Journal Article] CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice (2012)
  • Author(s): Dong L, Watanabe K, Itoh M, Huan CR, Tong XP, Nakamura T, Miki M, Iwao H, Nakajima A, Sakai T, Kawanami T, Sawaki T, Masaki Y, Fukushima T, Fujita Y, Tanaka M, Yano M, Okazaki T and Umehara H
  • Journal Title: International immunology Volume: 24 Pages: 327-337
  • DOI: 10.1093/intimm/dxs008
  • Peer Reviewed
• [Journal Article] Regulation of cell migration by sphingomyelin synthases : sphingomyelin in lipid rafts decreases responsiveness to signaling by the CXCL12/CXCR4 pathway (2012)
  • Author(s): Asano S, Kitatani K, Taniguchi M, Hashimoto M, Zama K, Mitsutake S, Igarashi Y, Takeya H, Kigawa J, Hayashi A, Umehara H and Okazaki T
  • Journal Title: Molecular and cellular biology Volume: 32 Pages: 3242-3252
  • DOI: 10.1128/MCB.00121-12
  • Peer Reviewed
• [Journal Article] Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice (2011)
  • Author(s): Yano M, Watanabe K, Yamamoto T, Ikeda K, Senokuchi T, Lu M, Kadomatsu T, Tsukano H, Ikawa M, Okabe M, Yamaoka S, Okazaki T, Umehara H, Gotoh T, Song WJ, Node K, Taguchi R, Yamagata K and Oike Y
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 3992-4002
  • DOI: 10.1074/jbc.M110.179176
  • Peer Reviewed
• [Journal Article] Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation (2011)
  • Author(s): Shakor AB, Taniguchi M, Kitatani K, Hashimoto M, Asano S, Hayashi A, Nomura K, Bielawski J, Bielawska A, Watanabe K, Kobayashi T, Igarashi Y, Umehara H, Takeya H and Okazaki T
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 36053-36062
  • DOI: 10.1074/jbc.M111.228593
  • Peer Reviewed
• [Journal Article] Inhibitory effects of dietary glucosylceramides on squamous cell carcinoma of the head and neck in NOD/SCID mice (2011)
  • Author(s): Fujiwara K, Kitatani K, Fukushima K, Yazama H, Umehara H, Kikuchi M, Igarashi Y, Kitano H and Okazaki T
  • Journal Title: International journal of clinical oncology / Japan Society of Clinical Oncology Volume: 16 Pages: 133-140
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21057846
  • Peer Reviewed