1997 Fiscal Year Annual Research Report

脳における血小板由来増殖因子(PDGF)の転写翻訳調節機構とPDGFの役割の解明

Research Project

Project/Area Number	08670246
Research Institution	Shiga University of Medical Science
Principal Investigator	笹原正清滋賀医科大学, 医学部, 助手 (20154015)
Keywords	血小板由来増殖因子 / 発達 / 脳 / mRNA / cloning / truncation / 神経賦活因子
Research Abstract	血小板由来増殖因子B鎖(PDGF-B)は、主として間葉系の細胞やグリア細胞に対する増殖因子として同定された。我々は、PDGF-Bが神経細胞に豊富に分布していることを見いだした。以来、中枢神経の調節、賦活、および損傷修復因子として重要であることを示してきた。前年度は、ラット脳を用いて、3.5kbと2.6kbの二種類のPDGF-B mRNAがあり、各々が独立して制御されていることを示した。本年度は、ラット新生仔脳cDNAライブラリーからRACEクローニングにより3.5kbのラットPDGF-B cDNAの全塩基配列を決定した。約1kbに及ぶ5側の非翻訳領域(UTS)は人やマウスと高いホモロジーを示し、人PDGF-B mRNAで報告されているような翻訳抑制作用を有することを推測した。同部には、複数のSP-1 promoter配列が見られた。さらに2.6kbのPDGF-B mRNAは、複数の転写開始点を有し、主としてsignal peptide開始点から15nt上流の部分でtruncationを受けた3.5kbのmRNAであった。発達ラット脳で、in situ hybridization等の方法により2.6kbのmRNA発現がPDGF-B蛋白発現に一致していることを示した。以上の事実は、翻訳抑制機能を有する5'UTSを欠いた2.6kbのmRNAを介して効率的に蛋白発現をするという、PDGF-B発現の新たな機構を示すものである。この発現機構は、生後のシナプス形成が活発に行われる時期や、急性の虚血時に観察され、脳の高次機能構築や、保護に重要な働きをしていることが強く疑われ、今後、さらに脳における2.6kbmRNA発現機構およびその機能的役割を解明する必要がある。本年は、血管内膜肥厚におけるPDGF-Bの役割を示した。他方で、新たな神経賦活因子検索の目的で、EGFファミリーであるHeparin-binding(HB-)EGFの発現をしらべた。EGFはin vitroで神経芽細胞増殖や分化に重要であるが、脳ではEGF発現は極めて限られている。本研究では、HB-EGFが脳EGF受容体のligandとして重要であることを示唆するものである。HB-EGFは腎臓にも分布することを示した。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Sasahara M: "Normaldeveloping rat brain expresses a platelet derived growth factor Bchain (c-sis) mRNA truncated at the S'end" Oncogene. (in press). (1998)
[Publications] Kaneko M: "The expression of Platelet-derived growth factor after transient forebrain ischemia in the gerbil hippocampus" Acta Neuro.Pathol.(in press). (1998)
[Publications] Hayase Y: "Expression of Heparin binding EGF-like growth factor in rat brain" Brain Res.(in press). (1998)
[Publications] 笹原正清: "血管病変における血小板由来増殖因子(PDGF)B鎖の発現解析" 血管と内皮. 7. 53-61 (1997)
[Publications] Nakagawa T: "Distribution of heparin-binding EGF-like growth factor protein and mRNA in the normal rat kidneys" Kidney Int.51. 1774-1779 (1997)
[Publications] Sasahara M.: "Analysis of platelet-derived growth factor B-chain and b-receptor expression after focal and transient ischemic cerebral insults" J.Stroke and Cerebrovascular Diseases. 6(1) Suppl.65-66 (1996)
[Publications] Mekada A: "Histochemical analysis of platelet-derived growth factor-B chain expression after transection of rat optic nerve" Acta Histochem.et Cytochem. 29,Suppl.1057-1058 (1996)
[Publications] Sasahara M: "Discrepancy between gene and protein expression revealed novel regulatory mechanism for platelet-derived growth factor B-chain expression in the developing brain" Acta Histochem.et Cytochem. 29,Suppl.1055-1056 (1996)
[Publications] Hayase Y: "Neuronal and glial expression of Heparin-binding EGF-like growth factor (HB-EGF) in rat brains" Acta Histochem.et Cytochem. 29,Suppl.1010-1011 (1996)
[Publications] Nakagawa T: "The expression site of Heparin-binding epidermal growth factor-like growth factor in normal rat kidney" Acta Histochem.et Cytochem. 29,Suppl.791-792 (1996)
[Publications] Hatsuda N: "Analysis of Heparin-binding EGF-like growth factor gene expression in the ischemic rat brain" Acta Histochem.et Cytochem. 29,Suppl.769-770 (1996)
[Publications] Amano S: "Development of a novel rat mutant with spontaneous limbic-like seizures" Am.J.Pathol.149. 329-336 (1996)
[Publications] Kataoka H: "Application of an isolated monolayer technique to peritoneal mesothelial cells : Immuno and enzyme histochemistry" Acta Cytologica. 39. 314 (1996)
[Publications] Uchida K: "Expression of platelet-derived growth factor B-chain in neointimal smooth muscle cells of balloon iniured rabbit femoral arteries" Atherosclerosis. 124. 9-23 (1996)
[Publications] Yang X: "Analysis of platelet-derived growth factor gene expression in cultured aortic endothelial cells from stroke-prone spontaneously hypertensive rats" J.Shiga Univ.Med.Sci.11. 5-16 (1996)
[Publications] Iihara K: "Induction of platelet-derived growth factor b-receptor in focal ischemia of rat brain" J.Cereb.Blood Flow Metab.16. 941-949 (1996)
[Publications] Sasahara M: "Ischemia induced platelet-derived growth factor B-chain and b-receptor expression in the brain" 18th Salzburg conference. 18. 12 (1995)

1997 Fiscal Year Annual Research Report

脳における血小板由来増殖因子(PDGF)の転写翻訳調節機構とPDGFの役割の解明

Principal Investigator

笹原 正清 滋賀医科大学, 医学部, 助手 (20154015)

Research Products

[Publications] Sasahara M: "Normaldeveloping rat brain expresses a platelet derived growth factor Bchain (c-sis) mRNA truncated at the S'end" Oncogene. (in press). (1998)

[Publications] Kaneko M: "The expression of Platelet-derived growth factor after transient forebrain ischemia in the gerbil hippocampus" Acta Neuro.Pathol.(in press). (1998)

[Publications] Hayase Y: "Expression of Heparin binding EGF-like growth factor in rat brain" Brain Res.(in press). (1998)

[Publications] 笹原正清: "血管病変における血小板由来増殖因子(PDGF)B鎖の発現解析" 血管と内皮. 7. 53-61 (1997)

[Publications] Nakagawa T: "Distribution of heparin-binding EGF-like growth factor protein and mRNA in the normal rat kidneys" Kidney Int.51. 1774-1779 (1997)

[Publications] Sasahara M.: "Analysis of platelet-derived growth factor B-chain and b-receptor expression after focal and transient ischemic cerebral insults" J.Stroke and Cerebrovascular Diseases. 6(1) Suppl.65-66 (1996)

[Publications] Mekada A: "Histochemical analysis of platelet-derived growth factor-B chain expression after transection of rat optic nerve" Acta Histochem.et Cytochem. 29,Suppl.1057-1058 (1996)

[Publications] Sasahara M: "Discrepancy between gene and protein expression revealed novel regulatory mechanism for platelet-derived growth factor B-chain expression in the developing brain" Acta Histochem.et Cytochem. 29,Suppl.1055-1056 (1996)

[Publications] Hayase Y: "Neuronal and glial expression of Heparin-binding EGF-like growth factor (HB-EGF) in rat brains" Acta Histochem.et Cytochem. 29,Suppl.1010-1011 (1996)

[Publications] Nakagawa T: "The expression site of Heparin-binding epidermal growth factor-like growth factor in normal rat kidney" Acta Histochem.et Cytochem. 29,Suppl.791-792 (1996)

[Publications] Hatsuda N: "Analysis of Heparin-binding EGF-like growth factor gene expression in the ischemic rat brain" Acta Histochem.et Cytochem. 29,Suppl.769-770 (1996)

[Publications] Amano S: "Development of a novel rat mutant with spontaneous limbic-like seizures" Am.J.Pathol.149. 329-336 (1996)

[Publications] Kataoka H: "Application of an isolated monolayer technique to peritoneal mesothelial cells : Immuno and enzyme histochemistry" Acta Cytologica. 39. 314 (1996)

[Publications] Uchida K: "Expression of platelet-derived growth factor B-chain in neointimal smooth muscle cells of balloon iniured rabbit femoral arteries" Atherosclerosis. 124. 9-23 (1996)

[Publications] Yang X: "Analysis of platelet-derived growth factor gene expression in cultured aortic endothelial cells from stroke-prone spontaneously hypertensive rats" J.Shiga Univ.Med.Sci.11. 5-16 (1996)

[Publications] Iihara K: "Induction of platelet-derived growth factor b-receptor in focal ischemia of rat brain" J.Cereb.Blood Flow Metab.16. 941-949 (1996)

[Publications] Sasahara M: "Ischemia induced platelet-derived growth factor B-chain and b-receptor expression in the brain" 18th Salzburg conference. 18. 12 (1995)

笹原正清滋賀医科大学, 医学部, 助手 (20154015)