2007 Fiscal Year Final Research Report Summary
EFFECTS OF ALL-TRANS RETINOIC ACID AND RETINOIDS ON ANGIOGENESIS
| Project/Area Number |
18591015
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAWARA Akira Tohoku University, TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR (90270834)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Sadayoshi TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, 大学院・医学系研究科, PROFESSOR (40271613)
SATO Yasufumi TOHOKU UNIVERSITY INSTITUTE OF DEVELOPMENT, AGING AND CANCER, PROFESSOR (50178779)
KAGECHIKA Hiroyuki TOKYO MEDICAL AND DENTAL UNIVERSITY, SCHOOL OF BIOMEDICAL SCIENCE, PROFESSOR (20177348)
SATO Akira TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER (20250764)
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| Project Period (FY) |
2006 – 2007
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| Keywords | all-trans retinoic acid / retinoic acid receptor / angiogenesis / retinoid / endothelial cells |
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| Research Abstract |
A natural retinoid all-trans retinoic acid (ATRA) regulates a variety of important cellular functions via retinoic acid receptor (RAR). ATRA has therapeutically been utilized against various malignancies including acute promyelocytic leukemia. Recently, ATRA has also been recognized to be beneficial against atherosclerotic vascular disorders. However, its effects on angiogenesis remain controversial. We therefore examined ATRA effects on in vitro angiogenesis in terms of capillary-like tube formation using human umbilical vein endothelial cells (HUVEC)/normal human dermal fibroblasts (NHDF) co-culture. ATRA as well as RAR agonist Am80 significantly induced capillary-like tube formation. The ATRA-induced tube formation was inhibited by co-incubation with RAR antagonist LE540/LE135. HUVEC proliferation, but not its migration, was also induced by ATRA. The ATRA-induced tube formation was completely abolished by co-incubation with vascular endothelial growth factor (VEGF) neutralizing antibody or with VEGF receptor (VEGFR)-2 (KDR) neutralizing antibody, but not with VEGFR-1 (Flt-1) neutralizing antibody. ATRA and Am80 induced VEGF gene promoter in NHDF was stimulated by ATRA, which was augmented by RAR overexpression. ATRA also induced VDGFR-2/KDR mRNA expression in HUVEC. Moreover, ATRA induced secretion of hepatocyte growth factor (HGF) as well as angiopoietin-2 (Ang-2) in the co-culture. Taken together, ATRA may have induced angiogenesis via RAR mainly by stimulation of HUVEC proliferation and enhancement of endogenous VEGF signaling, and in part by induction of HGF and Ang-2 production. Retinoids may therefore be potential candiadates for therapeutic angiogenesis against ischemic vascular disorders.
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Research Products
(153 results)
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[Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of endogenous vascular endothelial growth factor signaling.2007
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S
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Journal Title
Endocrinology 148
Pages: 1412-1423
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of endogenous vascular endothelial growth factor signaling2007
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S.
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Journal Title
Endocrinology 148
Pages: 1412-1423
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Embryonic lethality and impaired beta-cell replication by disruption of Reg receptor gene2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Sugihara K, Asano M, Yamauchi A, Yoshikawa T, Shervani NJ, Unno M, Sugawara A, Okamoto H
Organizer
43rd Annual Meeting of the European Association for the Study of Diabetes
Place of Presentation
Amsterdam
Year and Date
20070917-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Embryonic lethality and impaired beta-cell replication by disruption of Reg receptor gene.2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Sugihara K, Asano M, Yamauchi A, Yoshikawa T, Shervani NJ, Unno M, Sugawara A, Okamoto H
Organizer
43rd Annual Meeting of the European Association for the Study of Diabetes
Place of Presentation
Amsterdam
Year and Date
20070917-0921
Description
「研究成果報告書概要(和文)」より
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[Presentation] Impaired beta-cell replication in heterozygous mutant mice of Reg receptor gene2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Yamauchi A, Yoshikawa T, Shervani NJ, Sugihara K, Asano M, Unno M, Sugawara A, Okamoto H
Organizer
American Diabetes Association 67^<th> Scientific Sessions
Place of Presentation
Chicago
Year and Date
20070622-26
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Impaired beta-cell replication in heterozygous mutant mice of Reg receptor gene.2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Yamauchi A, Yoshikawa T, Shervani NJ, Sugihara K, Asano M, Unno M, Sugawara A, Okamoto H
Organizer
American Diabetes Association 67th Scientific Sessions
Place of Presentation
Chicago
Year and Date
20070622-0626
Description
「研究成果報告書概要(和文)」より
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[Presentation] Reduced β-cell proliferation and impaired glucose tolerance in pancreatic β-cell specific Extl3 knockout mice2007
Author(s)
Takahashi I, Nata K, Noguchi N, Ikeda T, YoshikawaT, Yamauchi A, Shervani NJ, Sugihara K, Asano M, Uruno A, Unno M, Takasawa S, Okamoto H, Sugawara A
Organizer
80th Annual Meeting of the Japanese Biochemical Society
Place of Presentation
Yokohama
Year and Date
2007-12-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] FK506 disruption impairs glucose-induced insulin secretion2007
Author(s)
Yoshikawa T, Noguchi N, Ikeda T, Takahashi I, Shervani NJ, Uruno A, Yamauchi A, Nata K, Takasawa S, Okamoto H, Sugawara A
Organizer
80th Annual Meeting of the Japanese Biochemical Society
Place of Presentation
Yokohama
Year and Date
2007-12-12
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of ATRA on angiogenesis2006
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Imaizumi M, Tsuchiya S, Ito S
Organizer
10th Meeting of the Society of Cardiovascular Endocrinology and Metabolism
Place of Presentation
Fukui
Year and Date
20061117-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Analyses of diabetes patients Who admitted to Tohoku Univ. Hosp. Dept. of Comp. Med.2006
Author(s)
Sugawara A, Gomi R, Kanatsuka H, Nagasaki Y, Ogawa S, Hinokio Y, Suzuki S, Katagiri H, Ito S, Oka Y, Hongo M
Organizer
49th Japan Diabetes Society Meeting
Place of Presentation
Tokyo
Year and Date
20060525-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of ATRA on angiogenesis2006
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Imaizumi M, Iinuma K, Ito S
Organizer
79th Japan Endocrine Society Meeting.
Place of Presentation
Kobe
Year and Date
20060519-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Medical interview training2006
Author(s)
Nagasaki Y, Sugawara A, Kanatsuka H, Hongo M
Organizer
38th Annual Meeting of the Japan Society, for Medical Education
Place of Presentation
Nara
Year and Date
2006-07-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Opinions of medical students2006
Author(s)
Kanatsuka H, Sugawara A, Nagasaki Y, Hongo M
Organizer
38th Annual Meeting of the Japan Society for Medical Education
Place of Presentation
Nara
Year and Date
2006-07-29
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Progress in Tohoku Univ. Hospital.2006
Author(s)
Igarashi H, Saijyou K, Ootake A, Machida Y, Watanabe S, Aoki M, Sugawara A, Sasaki I
Organizer
4th Conference on National Univ. Hospital.
Place of Presentation
Nagoya
Year and Date
2006-07-08
Description
「研究成果報告書概要(欧文)」より
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