ANALYSIS OF MOLECULAR MECHANISM FOR DIFFERENTIATION OF BOME-MARROW CELLS IN VASCULAR LESIONS

• Project/Area Number: 16590878
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: YOKODE Masayuki KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF CLINICAL INNOVATIVE MEDICINE, PROFESSOR, 医学研究科, 教授 (20252447)
• Co-Investigator(Kenkyū-buntansha): ARAI Hidenori KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRIC MEDICINE, ASSOCIATE PROFESSOR, 医学研究科, 講師 (60232021)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: ATHEROSCLEROSIS / STEM CELLS / ANGIOGENESIS / TRANSCRIPTION FACTOR / MORPHOGENESIS / THROMBOXANE / PROSTACYCLIN / REMODELING / 造血幹細胞 / メタボリックシンドローム / 骨髄由来血管前駆細胞 / 単球・マクロファージ / 血管平滑筋細胞 / 血管内皮細胞 / 血管再構築病変

Research Abstract

We studied atherogenesis and vascular remodeling. For this purpose, we administered functionally blocking antibody and clarified the molecular mechanism for differentiation of bone marrow (BM)-derived cells in the vascular lesion. We applied the experimental system to investigation of mesangial cell proliferation. We could demonstrate the effect of the administration of an anti-PDGF beta-receptor antibody (APB5) on glomerular cell proliferation and glomerulosclerosis. Furthermore, we could report a new function of CXCL16 as a novel angiogenic factor in HUVEC. Also, we studied the roles of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) in atherogenesis By cross-breeding atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP), we could demonstrate that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction. In addition, we investigated the functional roles of Smuc, snail-related transcription factor of muscle cells, at various stages of mouse development

Research Products

• [Journal Article] Plasma ghrelin levels in healthy elderly volunteers : the levels of acylated ghrelin in elderly females correlate positively with serum IGM-I levels and bowel movement frequency and negatively with systolic blood pressure (2006)
  • Author(s): T Akamizu, T Murayama, S Teramukai, K Miura, I Bando, T Irako, H Iwakura, H Ariyasu, H Hosoda, H Tada, A Matsuyama, S Kojima, T Wada, Y Wakatsuki, K Matsubayasi, T Kawakita, A Shimizu, M Fukushima, M Yokode, K Kangawa
  • Journal Title: Journal of Endocrinology 18 Pages: 333-344
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Plasma ghrelin levels in healthy elderly volunteers : the levels of acylated ghrelin in elderly females correlate positively with serum IGM-I levels and bowel movement frequency and negatively with systolic blood pressure (2006)
  • Author(s): T Akamizu, T Murayama, S Teramukai, K Miura, I Bando, T Irako, H Iwakura, H Ariyasu, H Hosoda, H Tada, A Matsuyama, S Kojima, T Wada, Y Wakatsuki, K Matsubayasi, T Kawakita, A Shimizu, M Fukushima, M Yokode, K Kangawa
  • Journal Title: Journal of Endocrinology. vol.188 Pages: 333-344
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Plasma ghrelin levels in healthy elderly volunteers : the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. (2006)
  • Author(s): Akamizu T, Murayama T, Teramukai S, Miura K, Bando I, Irako T, Iwakura H, Ariyasu H, Hosoda H, Tada H, Matsuyama A, Kojima S, Wada T, Wakatsuki Y, Matsubayashi K, Kawakita T, Shimizu A, Fukushima M, Yokode M, Kangawa K.
  • Journal Title: J Endocrinol. 188(2) Pages: 333-344
• [Journal Article] Activation of STAT3/Smad1 Is a Key Signaling Pathway for Progression to Glomerulosclerosis in Experimental Glomerulonephritis. (2005)
  • Author(s): Takahashi T, Abe H, Arai H, Matsubara T, Nagai K, Matsuura M, Iehara N, Yokode M, Nishikawa S, Kita T, Doi T.
  • Journal Title: The Journal of Biological Chemistry 280 Pages: 7100-7106
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of the novel Snai-related zinc-finger transcpiption factor gene Smuc during mouse development (2005)
  • Author(s): Zhuge X, Takaoka H, Tanaka M, Murayama T, Kawamoto T, Sano H, Togi K, Yamauti R, Ueda Y, Xu Y, Nishikawa S, Kita T, Yokode M.
  • Journal Title: International Journal of Molecular Medicine 15 Pages: 945-948
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Plasma asylated ghrelin levels correlate with subjective symptoms of fanctional dyspepsia in female patients (2005)
  • Author(s): Shinomiya T, Hukunaga M, Akamizu T, Irako T, Yokode M, Kangawa K, Nakai Y, Nakai Y.
  • Journal Title: Scandinavian Journal of Gastroenterology 40 Pages: 648-653
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CXCL 1 l6 is a novel angiogenic factor for human umbilical vein endothelial cells (2005)
  • Author(s): Zhuge X, Murayama T, Arai H, Yamauchi Y, Tanaka M, Simaoka T, Yonehara S, Kume N, Yokode M, Kita T.
  • Journal Title: Biochemical and Biophysical Research Communications 331 Pages: 1295-1300
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effects of Late Administration of Immunoglobulin on Experimental Atherosclerosis in Apolipoprotein E-Deficient Mice (2005)
  • Author(s): Okabe T, Kishimoto C, Shimada K, Murayama T, Yokode M, Kita T.
  • Journal Title: Circulation Journal 69 Pages: 1543-1546
  • NAID: 110003475381
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Attitudes of medical students and residents toward multidisciplinary team approach (2005)
  • Author(s): Tanaka M, Yokode M.
  • Journal Title: Blackwell Publishing 39 Pages: 1255-1256
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Serum Lipid Survey and its Recent Trend in the General Japanese Population in 2000 (2005)
  • Author(s): Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, Kita T.
  • Journal Title: J Arteriosclerosis Thrombosis 12 Pages: 98-106
  • NAID: 10018366076
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gas6 induces Akt/mTOR-mediated mesangial hypertrophy in diabetic nephropathy. (2005)
  • Author(s): Nagai K, Matsubara T, Mima A, Sumi E, Kanamori H, Iehara N, Fukatsu A, Yanagita M, Nakano T, Ishimoto Y, Kita T, Doi T, Arai H.
  • Journal Title: Kidney Int 68 Pages: 552-561
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of coagulation factor Xa and protease-activated receptor 2 in human mesangial cell proliferation. (2005)
  • Author(s): Tanaka M, Arai H, Liu N, Nogaki F, Nomura K, Kasuno K, Oida E, Kita T, Ono T.
  • Journal Title: Kidney Int 67 Pages: 2123-2133
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Establishment of a diabetic mouse model with progressive diabetic nephropathy. (2005)
  • Author(s): Inada A, Nagai K, Arai H, Miyazaki J, Nomura K, Kanamori H, Toyokuni S, Yamada Y, Bonner-Weir S, Weir GC, Fukatsu A, Seino Y.
  • Journal Title: Am J Pathol 167 Pages: 327-336
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Incidence of adverse drug reactions in geriatric units of university hospitals. (2005)
  • Author(s): Arai H, Akishita M, Teramoto S, Arai H, Mizukami K, Morimoto S, Toba K.
  • Journal Title: Geriat Gerontol Int 5 Pages: 293-297
  • NAID: 10018028310
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Survey of gene polymorphisms on four genes related to triglyceride and HDL-cholesterol in the general Japanese population in 2000. (2005)
  • Author(s): Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, Egashira T, Hattori H, Shirahashi N, Kita T.
  • Journal Title: J Arteriosclerosis Thrombosis. 12 Pages: 240-250
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of STAT3/Smad1 Is a Key Signaling Pathway for Progression to Glomerulosclerosis in Experimental Glomerulonephritis. (2005)
  • Author(s): Takahashi T, Abe H, Arai H, Matsubara T, Nagai K, Matsuura M, Jehara N, Yokode M, Nishikawa S, Kita T, Doi T.
  • Journal Title: The Journal of Biological Chemistry. vol.280 Pages: 7100-7106
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of the novel Snai-related zinc-finger transcpiption factor gene Smuc during mouse development (2005)
  • Author(s): Zhuge X, Takaoka H, Tanaka M, Murayama T, Kawamoto T, Sano H, Togi K, Yamauti R, Ueda Y, Xu Y, Nishikawa S, Kita T, Yokode M.
  • Journal Title: International Journal of Molecular Medicine. vol.15 Pages: 945-948
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Plasma asylated ghrelin levels correlate with subjective symptoms of fanctional dyspepsia in female patients (2005)
  • Author(s): Shinomiya T, Hukunaga M, Akamizu T, Irako T, Yokode M, Kangawa K, Nakai Y, Nakai Y
  • Journal Title: Scandinavian Journal of Gastroenterology. vol.40 Pages: 648-653
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CXCL 1 16 is a novel angiogenic factor for human umbilical vein endothelial cells (2005)
  • Author(s): Zhuge X, Murayama T, Arai H, Yamauchi R, Tanaka M, Simaoka T, Yonehara S, Kume N, Yokode M, Kita T.
  • Journal Title: Biochemical and Biophysical Research Communications. vol.331 Pages: 1295-1300
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of Late Administration of Immunoglobulin on Experimental Atherosclerosis in Apolipoprotein E-Deficient Mice (2005)
  • Author(s): Okabe T, Kishimoto C, Shimada K, Murayama T, Yokode M, Kita T.
  • Journal Title: Circulation Journal. vol.69 Pages: 1543-1546
  • NAID: 110003475381
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Attitudes of medical students and residents toward multidisciplinary team approach (2005)
  • Author(s): Tanaka M, Yokode M.
  • Journal Title: Blackwell Publishing vol.39 Pages: 1255-1256
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Serum Lipid Survey and its Recent Trend in the Genera Japanese Population in 2000 (2005)
  • Author(s): Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, Kita T.
  • Journal Title: J Arteriosclerosis Thrombosis. vol.12 Pages: 98-106
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gas6 induces Akt/mTOR-mediated mesangial hypertrophy in diabetic nephropathy. (2005)
  • Author(s): Nagai K, Matsubara T, Mima A, Sumi E, Kanamori H, Iehara N, Fukatsu A, Yanagita M, Nakano T, Ishimoto Y, Kita T, Doi T, Arai H.
  • Journal Title: Kidney Int. vol.68 Pages: 552-561
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of coagulation factor Xa and protease-activated receptor 2 in human mesangial cell proliferation. (2005)
  • Author(s): Tanaka M, Arai H, Liu N, Nogaki F, Nomura K, Kasuno K, Oida E, Kita T, Ono T.
  • Journal Title: Kidney Int. vol.67 Pages: 2123-2133
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Establishment of a diabetic mouse model with progressive diabetic nephropathy. (2005)
  • Author(s): Inada A, Nagai K, Arai H, Miyazaki J, Nomura K, Kanamori H, Toyokuni S, Yamada Y, Bonner-Weir D, Weir GC, Fukatsu A, Seino Y
  • Journal Title: Am J Pathol. vol.167 Pages: 327-336
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Incidence of adverse drug reactions in geriatric units of university hospitals. (2005)
  • Author(s): Arai H, Akishita M, Teramoto S, Arai H, Mizukami Morimoto D, Toba K.
  • Journal Title: Geriat Gerontol Int. vol.5 Pages: 293-297
  • NAID: 10018028310
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Survey of gene polymorphisms on four genes related to triglyceride and HDL-cholesterol in the general Japanese population in 2000. (2005)
  • Author(s): Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, Egashira T, Hattori H, Shirahashi N, Kita T.
  • Journal Title: J Arteriosclerosis Thrombosis. vol.12 Pages: 240-250
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells. (2005)
  • Author(s): Zhuge X, Murayama T, Arai H, Yamauchi R, Tanaka M, Shimaoka T, Yonehara S, Kume N, Yokode M, Kita T.
  • Journal Title: Biochem Biophys Res Commun. 331(4) Pages: 1295-1300
• [Journal Article] Expression of the novel Snai-related zinc-finger transcription factor gene Smuc during mouse development. (2005)
  • Author(s): Zhuge X, Kataoka H, Tanaka M, Murayama T, Kawamoto T, Sano H, Togi K, Yamauchi R, Ueda Y, Xu Y, Nishikawa S, Kita T, Yokode M.
  • Journal Title: Int J Mol Med. 15(6) Pages: 945-948
• [Journal Article] Activation of STAT3/Smad1 is a key signaling pathway for progression to glomerulosclerosis in experimental glomerulonephritis. (2005)
  • Author(s): Takahashi T, Abe H, Arai H, Matsubara T, Nagai K, Matsuura M, Iehara N, Yokode M, Nishikawa S, Kita T, Doi T.
  • Journal Title: J Biol Chem. 280(8) Pages: 7100-7106
• [Journal Article] Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice. (2005)
  • Author(s): Okabe TA, Kishimoto C, Shimada K, Murayama T, Yokode M, Kita T.
  • Journal Title: Circ J. 69(12) Pages: 1543-1546
  • NAID: 110003475381
• [Journal Article] Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients. (2005)
  • Author(s): Shinomiya T, Fukunaga M, Akamizu T, Irako T, Yokode M, Kangawa K, Nakai Y, Nakai Y.
  • Journal Title: Scand J Gastroenterol. 40(6) Pages: 648-653
• [Journal Article] Expression of the novel Snai-related zinc-finger transcription factor gene Smuc during mouse development (2005)
  • Author(s): Xin Zhuge, Masayuki Yokode, et al.
  • Journal Title: International Journal of Molecular Medicine (印刷中)
• [Journal Article] CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells (2005)
  • Author(s): Xin Zhuge, Hidenori Arai, Masayuki Yokode, et al.
  • Journal Title: Biochemical and Biophysical Research Communications (印刷中)
• [Journal Article] Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice. (2004)
  • Author(s): Xu Y, Arai H, Zhuge X, Hideto Sano, Murayama T, Yoshimoto M, Heike T, Nakahata T, Nishikawa S, Kita T, Yokode M.
  • Journal Title: Arterioscler Thromb Vasc Biol. 24 Pages: 477-482
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice. (2004)
  • Author(s): Kobayashi T, Tahara Y, Matsumoto M, Iguchi M, Sano H, Murayama T, Arai H, Oida H, Kobayashi Y, Jun K.Yamashita, Katagiri H, Majima M, Yokode M, Kita T, Narumiya S.
  • Journal Title: The Journal of Clinical Investigation 114 Pages: 784-794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Heidenhain Variant of Creutzfeldt-Jakob Disease : Diffusion-Weighted MRI and PET Characteristics (2004)
  • Author(s): Tsuji Y, Kanamori H, Murakami G, Yokode M, Mezaki T, Doh-ura K, Taniguchi K, Matsubayasi K, Hukuyama H, Kita T, Tanaka M.
  • Journal Title: Neuroimaging Journal 14 Pages: 63-66
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy. (2004)
  • Author(s): Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi M, Arai H, Nagata K, Kita T, Okamoto H, Yamamoto H, Doi T.
  • Journal Title: J Biol Chem 279 Pages: 19816-19823
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Type IV collagen is transcriptionally regulated by Smadl under advanced glycation end product (AGE) stimulation. (2004)
  • Author(s): Abe H, Matsubara T, Iehara N, Nagai K, Takahashi T, Arai H, Kita T, Doi T.
  • Journal Title: J Biol Chem 279 Pages: 14201-14206
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats. (2004)
  • Author(s): Ohashi S, Takagi H, Koyama S, Oh H, Watanabe D, Antonetti DA, Matsubara T, Nagai K, Arai H, Kita T, Honda Y.
  • Journal Title: Mol Vis 10 Pages: 608-617
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice. (2004)
  • Author(s): Xu Y, Arai H, Zhuge X, Sano H, Murayama T, Yoshimoto M, Heike T, Nakahata T, Nishikawa S, Kita T, Yokode M.
  • Journal Title: Arterioscler Thromb Vasc Biol. vol.24 Pages: 477-482
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice. (2004)
  • Author(s): Kobayashi T, Tahara Y, Matsumoto M, Iguchi M, Sano H.Murayama T, Arai H, Oida H, Yurugi-Kobayashi T, K.Yamashita J, Katagiri H, Majima M, Yokode M, Kita T, Narumiya S.
  • Journal Title: The Journal of Clinical Investigation. vol.114 Pages: 784-794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heidenhain Variant of Creutzfeldt-Jakob Disease : Diffusion-Weighted MRI and PET Characteristics (2004)
  • Author(s): Tsuji Y, Kanamori, H, Murakami G, Yokode M, Mezaki T, Doh-ura K, Taniguchi K, Matsubayasi K, Hukuyama H, Kita T, Tanaka M.
  • Journal Title: Neuroimaging Journal. vol.14 Pages: 63-66
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy. (2004)
  • Author(s): Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi M, Arai H, Nagata K, Kita T, Okamoto H, Yamamoto H, Doi T.
  • Journal Title: J Biol Chem. vol.279 Pages: 19816-19823
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Type IV collagen is transcriptionally regulated by Smad1 under advanced glycation end product (AGE) stimulation. (2004)
  • Author(s): Abe H, Matsubara T, Iehara N, Nagai K, Takahashi T, Arai H, Kita T, Doi T.
  • Journal Title: J Biol Chem. vol.279 Pages: 14201-14206
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats. (2004)
  • Author(s): Ohashi H, Takagi H, Koyama S, Oh H, Watanabe D, Antonetti DA, Matsubara T, Nagai K, Arai H, Kita T, Honda Y
  • Journal Title: Mol Vis. vol.10 Pages: 608-617
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects (2004)
  • Author(s): Takashi Akamizu, Masayuki Yokode, et al.
  • Journal Title: European Journal of Endocrinology 150 Pages: 447-455
• [Journal Article] Role of Bone Marrow-Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice (2004)
  • Author(s): Yang Xu, Hidenori Arai, Masayuki Yokode, et al.
  • Journal Title: Arteriosclerosis, Thrombosis and Vascular Biology 24 Pages: 477-482
• [Journal Article] Role of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice (2004)
  • Author(s): Takuya Kobayashi, Hidenori Arai, Masayuki Yokode, et al.
  • Journal Title: The Journal of Clinical Investigation 114 Pages: 784-794
• [Book] 血栓・止血・血管学(一瀬白帝編) (2005)
  • Author(s): 横出正之(共著)
  • Total Pages: 834
  • Publisher: 中外医学社