Development of novel PSGL-1 targeted agents for metabolic syndrome

• Project/Area Number: 24790927
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Okayama University
• Principal Investigator: HORIGUCHI Chikage 岡山大学, 医学部, 客員研究員 (40535192)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: メタボリックシンドローム / PSGL-1 / 接着分子 / 内臓脂肪 / インスリン抵抗性 / 肥満 / フコイダン

Research Abstract

Anti-PSGL-1 antibodies inhibited adipocyte hypertrophy and inflammation in white adipose tissue, and then ameliorated insulin resistance in type 2 diabetic mice. We separated and purified Fucoidan as a type of sulfated polysaccharides according to molecular weight. We are studying inhibition effects of each purified substances by using of monocytes-to-endothelial cells adhesion assay in vitro. We are going to determine the most effective substances for inhibiting cell adhesion, and then administer them to type 2 diabetic mice and study insulin resistance.

Research Products

• [Journal Article] Nuclear hormone receptor expression in mouse kidney and renal cell lines (2014)
  • Author(s): Ogawa D, Eguchi J, Wada J, Terami N, Hatanaka T, Tachibana H, Nakatsuka A, Horiguchi CS, Nishii N, Makino H
  • Journal Title: PLoS ONE Volume: 9(1) Issue: 1 Pages: e85594-e85594
  • DOI: 10.1371/journal.pone.0085594
  • NAID: 120005723280
  • Peer Reviewed
• [Journal Article] Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice (2014)
  • Author(s): Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horiguchi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H
  • Journal Title: Am J Physiol Renal Physiol Volume: 306(1)
  • Peer Reviewed
• [Journal Article] Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice. (2014)
  • Author(s): Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horiguchi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 1;306(1) Pages: 105-115
  • Peer Reviewed
• [Journal Article] The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO). (2013)
  • Author(s): Murakami K
  • Journal Title: Diab Vasc Dis Res Volume: 10(1) Issue: 1 Pages: 93-96
  • DOI: 10.1177/1479164112444640
  • Peer Reviewed
• [Journal Article] Telmisartan attenuates diabetic nephropathy by suppressing ixidative stress in db/db mice. (2013)
  • Author(s): Sato-Horiguchi C
  • Journal Title: Nephron Exp Nephrol Volume: 121(3-4) Issue: 3-4 Pages: 97-108
  • DOI: 10.1159/000343102
  • Peer Reviewed
• [Journal Article] Case of emphysematous cholecystitis in a patient with type 2 diabetes mellitus associated with schizophrenia (2012)
  • Author(s): Ogawa A, Shikata K, Uchida HA, Shinoura S, Yokomichi N, Ogawa D, Sato-Horiguchi C, Yagi T, Wada J, Makino H
  • Journal Title: J Diabetes Invest Volume: 3(6) Pages: 534-535
  • Peer Reviewed
• [Journal Article] Activation of liver x receptor inhibits osteopontin and ameliorates diabetic nephropathy. (2012)
  • Author(s): Tachibana H
  • Journal Title: J Am Soc Nephrol Volume: 23(11) Issue: 11 Pages: 1835-1846
  • DOI: 10.1681/asn.2012010022
  • Peer Reviewed
• [Journal Article] Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex (2012)
  • Author(s): Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Horiguchi CS, Ogawa D, Matsuki Y, Hiramatsu R, Yagita H, Kakuta S, Iwakura Y, Makino H
  • Journal Title: Diabetes Volume: 61(11) Issue: 11 Pages: 2823-2832
  • DOI: 10.2337/db12-0232
  • NAID: 120005300245
  • Peer Reviewed
• [Journal Article] Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage : anti-inflammatory effect of cholecystokinin (2012)
  • Author(s): Miyamoto S, Shikata K, Miyasaka K, Okada S, Sasaki M, Kodera R, Hirota D, Kajitani N, Takatsuka T, Kataoka HU, Nishishita S, Sato C, Funakoshi A, Nishimori H, Uchida HA, Ogawa D, Makino H
  • Journal Title: Diabetes Volume: 61(4) Issue: 4 Pages: 897-907
  • DOI: 10.2337/db11-0402
  • Peer Reviewed
• [Presentation] 糖尿病マウス腎および高糖濃度刺激下での培養腎細胞における核内受容体の発現解析 (2013)
  • Author(s): 寺見直人, 小川大輔, 堀口千景, 他
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本(熊本市現代美術館)
  • Year and Date: 2013-05-17
• [Presentation] 2型糖尿病における腎症の寛解および改善に関与する因子の解析 (2013)
  • Author(s): 小野哲一郎, 四方賢一, 堀口千景, 他
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本(熊本公徳会武道場)
  • Year and Date: 2013-05-16
• [Presentation] Liver X receptor agonist ameliorates diabetic nephropathy by inhibiting high glucose-induced osteopontin expression in proximal tubular epithelial cells (2012)
  • Author(s): Ogawa D, Tachibana H, Sato-Horiguchi C, et al
  • Organizer: AHA Scientific Sessions 2012
  • Place of Presentation: San Diego, California, USA
• [Presentation] 早期糖尿病性腎症におけるTelmisartan の抗酸化作用の検討 (2012)
  • Author(s): 堀口 千景, 他
  • Organizer: 第27回日本糖尿病合併症学会
  • Place of Presentation: 福岡(アクロス福岡)
• [Presentation] Liver X receptor agonist ameliorates diabetic nephropathy by inhibiting high glucose-induced osteopontin expression in proximal tubular epithelial cells (2012)
  • Author(s): Ogawa D, Tachibana H, Sato-Horiguchi C, et al
  • Organizer: ASN kidney Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Inhibition of PSGL-1 ameliorates obesity-related insulin resistance by prevention of inflammation in adipose tissue and liver in db/db mice (2012)
  • Author(s): Daisho Hirota, Chikage Sato, et al
  • Organizer: EASD 48th Annual Meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] 早期糖尿病性腎症におけるTelmisartan の抗酸化作用の検討 (2012)
  • Author(s): 佐藤 千景, 他
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜(パシフィコ横浜)
• [Presentation] PSGL-1 を阻害することにより, 肥満マウスにおける内臓脂肪と肝臓の炎症とインスリン抵抗性が抑制される (2012)
  • Author(s): 廣田 大昌, 佐藤 千景, 他
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜(パシフィコ横浜)
• [Presentation] 糖尿病性腎症モデルラットにおけるメタロチオネイン(metallothionein)の発現の検討 (2012)
  • Author(s): 橘 洋美, 佐藤 千景, 他
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜(パシフィコ横浜)
• [Presentation] 早期糖尿病性腎症におけるTelmisartanの抗酸化作用の検討 (2012)
  • Author(s): 佐藤 千景
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜（パシフィコ横浜）
• [Presentation] 早期糖尿病性腎症におけるTelmisartanの抗酸化作用の検討 (2012)
  • Author(s): 堀口 千景
  • Organizer: 第27回日本糖尿病合併症学会
  • Place of Presentation: 福岡（アクロス福岡）
• [Presentation] PSGL-1を阻害することにより，肥満マウスにおける内臓脂肪と肝臓の炎症とインスリン抵抗性が抑制される (2012)
  • Author(s): 廣田 大昌、佐藤 千景他
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜（パシフィコ横浜）
• [Presentation] Inhibition of PSGL-1 ameliorates obesity-related insulin resistance by prevention of inflammation in adipose tissue and liver in db/db mice. (2012)
  • Author(s): Daisho Hirota, Chikage Sato, et al.
  • Organizer: EASD 48th Annual Meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] 2型糖尿病における腎症の寛解および改善に関与する因子の解析
  • Author(s): 小野哲一郎、四方賢一、小比賀美香子、梶谷展生、小寺 亮、廣田大昌、村上和敏、堀口千景、小川大輔、和田 淳、片岡仁美、槇野博史
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本公徳会武道場（熊本県）
• [Presentation] 糖尿病マウス腎および高糖濃度刺激下での培養腎細胞における核内受容体の発現解析
  • Author(s): 寺見直人、小川大輔、橘 洋美、堀口千景、小寺 亮、江口 潤、中司敦子、和田 淳、四方賢一、槇野博史
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市現代美術館（熊本県）
• [Book] 糖尿病×CKD 診療ガイド Q&A (2012)
  • Author(s): 堀口 千景
  • Publisher: 南山堂
• [Book] 糖尿病×CKD 診療ガイド Q&A (2012)
  • Author(s): 堀口 千景
  • Total Pages: 179
  • Publisher: 南山堂