1999 Fiscal Year Annual Research Report

メサンギウム細胞特異遺伝子megsinの細胞特異的転写制御機構とその臨床応用

Research Project

Project/Area Number	11671053
Research Institution	Tokai University
Principal Investigator	稲城玲子東海大学, 総合医学研究所, 講師 (50232509)
Co-Investigator(Kenkyū-buntansha)	宮田敏男東海大学, 総合医学研究所, 助教授 (10222332)
Keywords	進行性糸球体障害 / メサンギウム細胞 / serpin / megsin / promoter / メサンギウム細胞特異的転写調節機構 / メサンギウム細胞 / 特異的DNA結合蛋白
Research Abstract	我々は、進行性糸球体障害の分子メカニズム解明に関する研究を進めるなか、ヒトメサンギウム細胞に高発現する新規遺伝子、megsinのcloningに成功した。Megsinはserine protease inhibitor(serpin)superfamilyに属する遺伝子で、既知のserpinが細胞外基質の代謝、細胞分化・増殖など多様な生理活性を有することから、megsinも糸球体の構造や機能調節に関する重要な役割を担っていることが示唆される。事実、ヒトメサンギウム細胞増殖性IgA腎症及びラットThy-1腎炎モデルにおいはmegsinの発現が亢進することを報告している。本研究では、megsinを人為的転写制御することによる糸球体疾患発症・進展抑制の可能性、あるいはmegsinのメサンギウム細胞特異的転写領域を用いた糸球体特異的gene targeting法の確立などを目指し、megsin転写調節機構の解明を進めてきた。これまでのところ、megsinのゲノム構造(全長20kpb、8個のexonから構成)、megsin転写開始点、及びその上流約1.6kbpの塩基配列などを決定し、megsin転写開始点-1079から-927にエンハンサー領域、あるいは-128から-121にコアプロモーター領域と思われる正の転写調節領域が存在することを明らかにした。更にこの転写開始点上流域約1.6kbpの各種細胞における転写活性を比較すると、ヒト線維芽細胞や血管内皮細胞などに比し、メサンギウム細胞内で高い活性を示すことも判明した。同時にゲルシフト法にて、コアプロモーター領域と思われる領域にはメサンギウム細胞特異的なDNA結合蛋白が他の細胞由来DNA結合蛋白に比し、高率に結合するも示された。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Miyata T et. al: "Diagnosis, pathogenesis, and treatment of dialysis-related amyloidosis"Miner Electrolyte Metab. 25. 114-117 (1999)
[Publications] Miyata T et. al: "2-Isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide (OPB-9195) inhibits the neointima proliferation of rat carotid artery following balloon injury: Role of glvcoxidation and lipoxidation reactions in vascular tissue damage"FEBS letter. 445. 202-206 (1999)
[Publications] Izuhara Y et. al: "A sensitive and specific ELISA for plasma pentosidine"Nephrol Dial Transplant. 14. 576-580 (1999)
[Publications] Suzuki D et. al: "Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic giomerular lesions"J Am Soc Nephrol. 10. 822-832 (1999)
[Publications] Miyata T et. al: "Increased carbonyl modification by lipids and carbohydrates in diabetic nephropathy"Kidney Int. 56(Supple71). s54-s56 (1999)
[Publications] Miyata T et. al: "Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney"J Am Soc Nephrol. 10. 1590-1595 (1999)
[Publications] Inagi R et. al: "Oxdative protein damage with carbohydrates and lipids in uremia: "carbonyl stress""Blood Purification. 17. 95-98 (1999)
[Publications] Suzuki D et. al: "Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases"J Am Soc Nephrol. (in press).
[Publications] Miyata T et. al: "Mechanism of inhibitory effect of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide (OPB-9195) on AGE and ALE formation"J Am Soc Nephrol. (in press).
[Publications] Miyata T et. al: "Advanced glycation and lipoxidation of the peritoneal membrane in peritoneal dialysis: Respective contribution of serum and peritoneal dialysis fluid reactive carbonyl compounds"Kidney Int. (in press).
[Publications] Inagi R et. al: "Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: Role in the pathogenesis of peritoneal membrane dysfunction in peritoneal dialysis"FEBS letter. (in press).
[Publications] Miyata T et. al: "Redox Regulation of Cell Signaling and Its Clinical Application."MARCEL DEKKER INC. 10 (1999)

1999 Fiscal Year Annual Research Report

メサンギウム細胞特異遺伝子megsinの細胞特異的転写制御機構とその臨床応用

Principal Investigator

稲城 玲子 東海大学, 総合医学研究所, 講師 (50232509)

Research Products

[Publications] Miyata T et. al: "Diagnosis, pathogenesis, and treatment of dialysis-related amyloidosis"Miner Electrolyte Metab. 25. 114-117 (1999)

[Publications] Miyata T et. al: "2-Isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide (OPB-9195) inhibits the neointima proliferation of rat carotid artery following balloon injury: Role of glvcoxidation and lipoxidation reactions in vascular tissue damage"FEBS letter. 445. 202-206 (1999)

[Publications] Izuhara Y et. al: "A sensitive and specific ELISA for plasma pentosidine"Nephrol Dial Transplant. 14. 576-580 (1999)

[Publications] Suzuki D et. al: "Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic giomerular lesions"J Am Soc Nephrol. 10. 822-832 (1999)

[Publications] Miyata T et. al: "Increased carbonyl modification by lipids and carbohydrates in diabetic nephropathy"Kidney Int. 56(Supple71). s54-s56 (1999)

[Publications] Miyata T et. al: "Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney"J Am Soc Nephrol. 10. 1590-1595 (1999)

[Publications] Inagi R et. al: "Oxdative protein damage with carbohydrates and lipids in uremia: "carbonyl stress""Blood Purification. 17. 95-98 (1999)

[Publications] Suzuki D et. al: "Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases"J Am Soc Nephrol. (in press).

[Publications] Miyata T et. al: "Mechanism of inhibitory effect of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide (OPB-9195) on AGE and ALE formation"J Am Soc Nephrol. (in press).

[Publications] Miyata T et. al: "Advanced glycation and lipoxidation of the peritoneal membrane in peritoneal dialysis: Respective contribution of serum and peritoneal dialysis fluid reactive carbonyl compounds"Kidney Int. (in press).

[Publications] Inagi R et. al: "Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: Role in the pathogenesis of peritoneal membrane dysfunction in peritoneal dialysis"FEBS letter. (in press).

[Publications] Miyata T et. al: "Redox Regulation of Cell Signaling and Its Clinical Application."MARCEL DEKKER INC. 10 (1999)

稲城玲子東海大学, 総合医学研究所, 講師 (50232509)