Regulation of cellular cytoskeleton by the soluble LDL receptor family with the application for novel anti-atherosclerosis therapy

• Project/Area Number: 21390277
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University
• Principal Investigator: BUJO Hideaki 千葉大学, 大学院・医学研究院, 教授 (80291300)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 脂質代謝異常 / 単球 / 平滑筋細胞 / 細胞遊走 / LR11 / 細胞骨格 / 脂肪細胞 / 運動能 / 動脈硬化 / 血管傷害

Research Abstract

Soluble form of LR11, a member of LDL receptor family, plays an important role in the pathological phenotypic conversion of intimal smooth muscle cells. The aim of study was to clarify the mechanism underlying the regulation of cytoskeleton reorganization to achieve the acceleration of cellular migration and adhesion through the LR11-mediated pathways, the involvement of sLR11 in various diseases, and the basic significance for the development of novel therapy against atherosclerosis. The results obtained from the cell-biological, animal or patient analysis has shown that soluble LR11 is important for the common mechanism underlying the migration for floating cells as well as attached cells, the differentiation of adipocytes, and the development of vascular injury. These results suggested that the target regulation focused on the molecule contributes to the development of novel therapy to regulate the cell migration in the fields of atherosclerosis and also in other diseases.

Research Products

• [Journal Article] Enhancved cir-culating soluble LR11 in patients with diabetic retinopathy (2012)
  • Author(s): Takahashi M, Bujo H, Shiba T, Jiang M, Maeno T, Shirai K
  • Journal Title: Am J Ophthalmol Volume: (in press)
  • Peer Reviewed
• [Journal Article] BACE1 activity is re-lated to CSF concentrations of SORL1, soluble amyloid precursor protein and tau (2012)
  • Author(s): Tsolakidou A, Alexopoulos P, Guo L-H, Guo, Grimmer T, Westerteicher C, Kratzer M, Jiang M, Bujo H, Rosselli F, Leante MR, Livrea P, Kurz A, Perneczky R
  • Journal Title: Alzheimers Dement Volume: (in press)
  • Peer Reviewed
• [Journal Article] SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer's disease (2012)
  • Author(s): Guo L-H, Guo, Westerteicher C, Wang X-H, Kratzer M, Tsolakidou A, Jiang M, Grimmer T, Laws SM, Alexopoulos P, Bujo H, Kurz A, Perneczky R
  • Journal Title: Eur Arch Psychiatry Clin Neurosci Volume: (in press)
  • Peer Reviewed
• [Journal Article] Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system (2012)
  • Author(s): Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Saito Y, Satoh Y, Bujo H
  • Journal Title: Exp Mol Med Volume: (in press)
  • Peer Reviewed
• [Journal Article] Fibrin glue is a candidate scaffold for long-term therapeutic protein expression in spontaneously differentiated adipocytes in vitro (2012)
  • Author(s): Aoyagi Y, Kuroda M, Asada S, Tanaka S, Konno S, Tanio T, Aso M, Okamoto Y, Nakayama T, Saito Y, Bujo H
  • Journal Title: Exp Cell Res Volume: 318 Issue: 1 Pages: 8-15
  • DOI: 10.1016/j.yexcr.2011.10.007
  • Peer Reviewed
• [Journal Article] Enhanced circulating soluble LR11 in patients with diabetic retinopathy (2012)
  • Author(s): Takahashi M, Bujo H, Shiba T, Jiang M, Maeno T, Shirai K
  • Journal Title: Am J Ophthalmol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Interrelations between CSF soluble APP, amyloid-b 1-42, SORL1, and tau levels in Alzheimer's disease (2011)
  • Author(s): Alexopoulos P, Luo L-H, Tsolakidou A, Kratzer M, Grimmer T, Westerteicher C, Jiang M, Bujo H, Diehl-Schmid J, Kurz A, Perneczky R
  • Journal Title: J Alzheimers Dis Volume: 28(3) (in press)
  • Peer Reviewed
• [Journal Article] Adipocytes as a vehicle for ex vivo gene therapy Novel replacement the rapy for diabetes and other metabol ic diseases (2011)
  • Author(s): Kuroda M, Bujo H, Aso M, Saito Y
  • Journal Title: J Diabet Invest Volume: 2 Issue: 5 Pages: 333-340
  • DOI: 10.1111/j.2040-1124.2011.00133.x
  • Peer Reviewed
• [Journal Article] Ceiling culture-derived proliferative adipocytes retain high a dipogenic potential suitable for use as a vehicle for gene transduction therapy (2011)
  • Author(s): Asada S, Kuroda M, Aoyagi Y, Fukaya Y, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, Bujo H
  • Journal Title: Am J Physiol Cell Physiol Volume: 301
  • Peer Reviewed
• [Journal Article] Fibrin glue increases the cell survival and the transduced gene product secretion of the ceiling culture-derived adipocytes trans-planted in mice (2011)
  • Author(s): Aoyagi Y, Kuroda M, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, Saito Y
  • Journal Title: Exp Mol Med Volume: 243 Issue: 3 Pages: 161-167
  • DOI: 10.3858/emm.2011.43.3.021
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary crystallographic anal-ysis of human LR11 Vps10p domain (2011)
  • Author(s): Nakata Z, Nagae M, Yasui N, Bujo H, Nogi T, Takagi J
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun Volume: 67 Issue: 1 Pages: 129-132
  • DOI: 10.1107/s1744309110048153
  • Peer Reviewed
• [Journal Article] Ceiling culture-derived proliferative adipocytes retain high adipogenic potential suitable for use as a vehicle for gene transduction therapy (2011)
  • Author(s): Asada S, Kuroda M, Aoyagi Y, Fukaya Y, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, Bujo H
  • Journal Title: Am J Physiol Cell Physiol Volume: 301 Issue: 1 Pages: C181-C185
  • DOI: 10.1152/ajpcell.00080.2011
  • Peer Reviewed
• [Journal Article] Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are improved by the lecithin : cholesterol acyltransferase produced by gene-transduced adipocytes in vitro (2011)
  • Author(s): Asada, S., Kuroda, M., Aoyagi, Y., Bujo, H., Tanaka, S., Konno, S., Tanio, M., Ishii, I., Aso, M., Saito, Y.
  • Journal Title: Mol Genet Metab. Volume: 102 Pages: 229-231
  • Peer Reviewed
• [Journal Article] Enhanced circu-lating soluble LR11 in patients with coronary organic stenosis (2010)
  • Author(s): Takahashi M, Bujo H, Jiang M, Noike H, Saito Y, Shirai K
  • Journal Title: Athero-sclerosis Volume: 210 Pages: 581-584
  • URL: http://dx.doi.org/10.1016/j.atherosclerosis.2009.12.010
  • Peer Reviewed
• [Journal Article] Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Patients with Alzheimer Disease (2010)
  • Author(s): Ikeuchi T, Hirayama S, Miida T, Fukamachi I, Tokutake T, Ebinuma H, Takubo K, Kaneko H, Kasuga K, Kakita A, Takahashi H, Bujo H, Saito Y, Nishizawa M
  • Journal Title: Dement Geriatr Cogn Disord Volume: 30 Issue: 1 Pages: 28-32
  • DOI: 10.1159/000315539
  • Peer Reviewed
• [Journal Article] Enhanced circulating soluble LR11 in patients with coronary organic stenosis. (2010)
  • Author(s): Takahashi M, Bujo H, Jiang M, Noike H, Saito Y, Shirai K.
  • Journal Title: Atherosclerosis Volume: 210(2) Pages: 581-584
  • Peer Reviewed
• [Journal Article] Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Patientswith Alzheimer Disease. (2010)
  • Author(s): Ikeuchi, T., Hirayama, S., Miida, T., Fukamachi, I., Tokutake, T., Ebinuma, H., Takubo, K., Kaneko, H., Kasuga, K., Kakita, A Takahashi, H., Bujo, H., Saito, Y., Nishizawa, M.
  • Journal Title: Dement Geriatr Cogn Disord. Volume: 30 Pages: 28-32
  • Peer Reviewed
• [Journal Article] Enhanced circulating solubule LR11 in patients with coronary organic stenosis. (2010)
  • Author(s): Takahashi M, Bujo H, Jiang M, Noike H, Saito Y, Shirai K.
  • Journal Title: Atherosclerosis Volume: 210(2) Pages: 581-584
  • Peer Reviewed
• [Journal Article] Development of an immunoassay for the quantification of soluble LR11, a circu-lating marker of atherosclerosis (2009)
  • Author(s): Matsuo M, Ebinuma H, Fukamachi I, Jiang M, Bujo H, Saito Y
  • Journal Title: Clin Chem Volume: 55 Issue: 10 Pages: 1801-1808
  • DOI: 10.1373/clinchem.2009.127027
  • Peer Reviewed
• [Journal Article] Development of an immunoassay for the quantification of solbule LR11, A circulating marker of atherosclerosis. (2009)
  • Author(s): Matsuo M, Ebinuma H, Fukamachi I, Jiang M, Bujo H, Saito Y.
  • Journal Title: Cline Chem Volume: 55(10) Pages: 1801-8
  • Peer Reviewed
• [Journal Article] Plasma pre beta1-HDL level is elevated in unstable angina pectoris. (2009)
  • Author(s): Tashiro J, Miyazaki O, Nakamura Y, Miyazaki A, Fukamachi I, Bujo H, Saito Y.
  • Journal Title: Atherosclerosis Volume: 204(2) Pages: 595-600
  • Peer Reviewed