Treatment of intestinal fibrosis of Crohn disease by regulation of expression of glycan chains

• Project/Area Number: 24590938
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: SUZUKI Kenji 新潟大学, 医歯学総合病院, 講師 (00303123)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: siRNA / 線維化 / 糖鎖 / クローン病 / 消化管狭窄

Outline of Final Research Achievements

We have revealed that the carbohydrate sulphotransferase CHST15 gene plays an important role in intestinal fibrosis in Crohn's disease, and developed a siRNA drug, STNM01, which selectively inhibits the expression of the gene, collaborating with the Stelic Institute of Regenerative Medicine, Tokyo.
In this study, we have revealed that this new siRNA drug inhibited the progression of fibroblasts into myofibroblasts, and decresed the collagen production by fibroblasts, and that STNM01 could ameliorate chronic fibrosing DSS colitis. Additionally, we have revealed the overexpression of CHST15 in the colon of patients with Crohn's diseasae, suggesting that CHS15 could be a promissing target of the siRNA drug for the treatment of intestinal fibrosis in Crohn's disease.

Research Products

• [Journal Article] Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium. (2015)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin MR, Miyashita S, Nomoto M, Harima M, Suzuki H, Nakamura T, Nakamura M, Suzuki K, Watanabe K.
  • Journal Title: Cytokine Volume: 15 Issue: 2 Pages: 305-312
  • DOI: 10.1016/j.cyto.2015.03.017
  • Peer Reviewed
• [Journal Article] Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy. (2015)
  • Author(s): Watanabe K, Arumugam S, Sreedhar R, Thandavarayan RA, Nakamura T, Nakamura M, Harima M, Yoneyama H, Suzuki K.
  • Journal Title: Cell Signal Volume: 15 Issue: 7 Pages: 1517-1524
  • DOI: 10.1016/j.cellsig.2015.03.004
  • Peer Reviewed
• [Journal Article] Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling. (2015)
  • Author(s): Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, Watanabe K, Konishi T.
  • Journal Title: PLoS One Volume: 2015 Issue: 3 Pages: 1-18
  • DOI: 10.1371/journal.pone.0119214
  • Peer Reviewed / Open Access
• [Journal Article] Dominant trait linked to chromosome 1 in DBA/2 mice for the resistance to autoimmune gastritis appears in bone marrow cells. (2014)
  • Author(s): Fujii M, Suzuki K, Suenaga S, Wakatsuki M, Kushida Y, Touma M, Hosono M.
  • Journal Title: Exp Anim Volume: 63 Pages: 155-167
  • NAID: 130003391616
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olmesartan protects against oxidative stress possibly through the Nrf2 signaling pathway and inhibits inflammation in dauronorubicin-induced nephrotoxicity in rats. (2014)
  • Author(s): Gounder VK, Arumugam S, Arozal W, Thandavarayan R, Pitchaimani V, Harima M, Suzuki K, Nomoto M, Watanabe K.
  • Journal Title: Int Immunopharm Volume: 18 Issue: 2 Pages: 282-289
  • DOI: 10.1016/j.intimp.2013.11.018
  • Peer Reviewed
• [Journal Article] Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK-mdediated apoptosis. (2013)
  • Author(s): Arumugam S, Mito S, Thandavarayan RA, Giridharan VV, Pitchaimani V, Karuppagounder V, Harima M, Nomoto M, Suzuki K, Watanabe K.
  • Journal Title: Cardiovasc Ther Volume: 31 Issue: 6 Pages: 352-362
  • DOI: 10.1111/1755-5922.12029
  • Peer Reviewed
• [Journal Article] ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma. (2013)
  • Author(s): Nagata M, Noman AA, Suzuki K, Kurita H, Ohnishi M, Ohyama T, Kitamura N, Kobayashi T, Uematsu K, Takahashi K, Kodama N, Kawase T, Hoshina H, Ikeda N, Shingaki S, Takagi R
  • Journal Title: BMC Cancer Volume: 13 Issue: 1 Pages: 410-410
  • DOI: 10.1186/1471-2407-13-410
  • Peer Reviewed
• [Journal Article] A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. (2013)
  • Author(s): Fujii M, Kenichi Watanabe et al.
  • Journal Title: Med Mol Morphol. Volume: in press Issue: 3 Pages: 141-152
  • DOI: 10.1007/s00795-013-0016-1
  • NAID: 10031203181
  • Peer Reviewed
• [Journal Article] Tissue culture of human alveolar periosteal sheets using a stem-cell culture medium (MesenPRO-RS™): In vitro expansion of CD146-positive cells and concomitant upregulation of osteogenic potential in vivo. (2013)
  • Author(s): Uematsu K, Kawase T, Nagata M, Suzuki K, Okuda K, Yoshie H, Burns DM, Takagi R.
  • Journal Title: Stem Cell Res. Volume: 10(1) Issue: 1 Pages: 1-19
  • DOI: 10.1016/j.scr.2012.08.006
  • Peer Reviewed
• [Journal Article] The hyperglycemia stimulated myo-cardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic non-obese type 2 diabetic rats : a differential role of unfolded protein response (UPR) signaling proteins (2013)
  • Author(s): Lakshmanan AP, Harima M, Suzuki K, Soetikno V, Nagata M, Nakamura T, Takahashi T, Sone H, Kawachi H, Watanabe K
  • Journal Title: Int J Biochem Cell Biol Volume: 45 Issue: 2 Pages: 438-447
  • DOI: 10.1016/j.biocel.2012.09.017
  • Peer Reviewed
• [Journal Article] Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway (2012)
  • Author(s): Soetikno V, Sari FR, Lakshmanan AP, Arumugam S, Harima M, Suzuki K, Kawachi H, Watanabe K
  • Journal Title: Mol Nutr Food Res Volume: 57 Issue: 9 Pages: 1649-1659
  • DOI: 10.1002/mnfr.201200540
  • Peer Reviewed
• [Journal Article] Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium. (2012)
  • Author(s): Yamaguchi H et al.
  • Journal Title: Med Mol Morphol Volume: 45 Issue: 3 Pages: 140-151
  • DOI: 10.1007/s00795-011-0550-7
  • Peer Reviewed
• [Journal Article] A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells : coordinated activation of bone formation and resorption (2012)
  • Author(s): Masaki Nagata
  • Journal Title: Bone Volume: 50 Issue: 5 Pages: 1123-1129
  • DOI: 10.1016/j.bone.2012.02.631
  • Peer Reviewed
• [Journal Article] Role of protein kinase C-MAPK, oxidative stress and inflammation pathways in diabetic nephropathy. (2012)
  • Author(s): Soetikono V, Watanabe K, Lakshamanan AP, Arumugam S, Sari FR, Sukumaran V, Thandavarayan RA, Harima M, Suzuki Ket al.
  • Journal Title: J Neprol Therapeutic Volume: S2 Issue: 01 Pages: 1-1
  • DOI: 10.4172/2161-0959.s2-001
  • Peer Reviewed
• [Presentation] Endoscopic submucosal injection of a synthesized anti-CHST15 dsRNA for sulfated glycosaminoglycan is a safe and beneficial treatment for patients with Crohn's disease who do not respond sufficiently to the conventional treatment. (2014)
  • Author(s): Suzuki K, Yokoyama J, Kawachi Y, Honda Y, Asakura H, Okazaki K, Suzuki Y, Sameshima Y, Fukushima T, Fujii M, Hashiguchi T, Mizumoto S, Sugahara K, Yoenayma H.
  • Organizer: 2014 Digestive disease week, Chicago, USA.
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-05-04
• [Book] Vimentin: Concepts and molecular mechanisms (2013)
  • Author(s): Suzuki K, Nagata M, Kawase T, Uematsu K, Honda Y, Kawauchi Y, Yokoyama J, Arumugam S, Thandavarayan RA, Yoneyama H, Watanabe K, Asakura H.
  • Total Pages: 174
  • Publisher: Nova Science Publishers, Inc.
• [Book] Mast cells. Phenotypic features, biological functions and role in immunity. (2013)
  • Author(s): Suzuki K, Nagata M, Kawase T, Uematsu K, Honda Y, Kawauchi Y, Yokoyama J, Arumugam S, Thandavarayan RA, Yoneyama H, Watanabe H, Asakura H.
  • Total Pages: 301
  • Publisher: Nova Science Publishers, Inc.