1999 年度実績報告書

メサンギウム細胞特異発現遺伝子群の機能解析及びその病因論に関する研究

研究課題

研究課題/領域番号	11307016
研究種目	基盤研究(A)
研究機関	東海大学
研究代表者	黒川清東海大学, 医学部, 教授 (30167390)
研究分担者	稲城玲子東海大学, 総合医学研究所, 講師 (50232509) 宮田敏男東海大学, 総合医学研究所, 助教授 (10222332)
キーワード	3'-directed / cDNA / library法 / メサンギウム細胞 / メサンギウム細胞特異的遺伝子 / megsin / 進行性糸球体疾患 / 分子生物学
研究概要	従来、細胞特異的遺伝子の同定にはsubtraction library法やdifferential hybridization法などが用いられてきたが、いずれも定量性に欠き、手技的な条件設定の困難さが残されている。そこで我々は、ヒトメサンギウム細胞について、より定量的で、なおかつ細胞特異的遺伝子を検出しやすいcDNAライブラリーの作製を考慮し、近年確立された3'-directed cDNA library法を起用した。この独創的な分子生物学的アプローチによって、以下に示すいくつかの興味深い研究成果が得られた。1)世界に先駆け、ヒトメサンギウム細胞に発現する遺伝子群の定量的解析を行い、細胞特性の一部を分子レベルで明らかにすることに成功し、その中から5つの未知のメサンギウム細胞特異的遺伝子(megsin, meg genesと命名)の単離・同定を行った。2)megsinはメサンギウム細胞に高発現し、既知のセンリプロテアーゼインヒビター(serpin)と高い相同性を有する未知の蛋白をコードする新規遺伝子で、メサンギウム増殖性IgA腎症でその発現が亢進する。3)Meg genes(meg-1,meg-2,meg-3,meg-4)はmegsinと同様、メサンギウム細胞に特異的に高発現し、いずれも未知の蛋白をコードする遺伝子である。これらはアミノ酸レベルで特徴的なモチーフを有することが明らかとなり、既知のalkarine phosphatase,転写調節因子、ATP依存性metalloproteaseとの類似の構造,機能を有する可能性が示唆された。これまでにラット、マウスにおいてmegs genes相同遺伝子が存在することもあきらかにしており、Tg/KOマウスを用いたmegs機能解析や新たな腎疾患モデル動物樹立の可能性なども検討している。

研究成果
(29件)

すべてその他

すべて文献書誌 (29件)

[文献書誌] Ahkand AA et al.: "Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase p60_<c-src>"J Cellular Biochemistry. 72. 1-7 (1999)
[文献書誌] Miyata T et al.: "Alterations in non-enzymatic biochemistry in uremia : Origin and significance of "carbonyl stress"in long-term uremic complications"Kidney Int. 55. 389-399 (1999)
[文献書誌] Miyata T et al.: "Diagnosis,Pathogenesis,and treatment of dialysis-related amyloidosis"Miner Electrolyte Metab. 25. 114-117 (1999)
[文献書誌] Wada T et al.: "Implication of Carbonyl stress in long-term uremic complications"Nephrol Sial Transplant. Supple 1. 79-81 (1999)
[文献書誌] 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 glycoxidation and lipoxidation reactions in vascular tissue damage"FEBS letter. 445. 202-206 (1999)
[文献書誌] Miyata T et al.: "Carbonyl stress : Increased carbonyl modification of tissue and cellular proteins in uremi"Perit Dial Int. 19[Supple 2]. 58-61 (1999)
[文献書誌] Stein G et. al: "Decrease in serum pentosidine levels of ESRD patients during polysulfone hemodialysis"Nephrol Dial Transplant. 14. 1606-1608 (1999)
[文献書誌] Liu W et al.: "4-Hydroxynonenal triggers an epidermal growth factor receptorlinked signal pathway for growth inhibition"J Cel Sci. 112. 2409-2407 (1999)
[文献書誌] Kawada N et al.: "Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction"Kidney Int. 56. 1004-1013 (1999)
[文献書誌] Nangaku M et al.: "Possible involvement of "carbonyl stress"in the pathogenesis of dialysis-related amyloidosis"Am J Med Sci. 317. 410-415 (1999)
[文献書誌] Suzuki D et al.: "Carbonyl stress and diabetic nephropathy"Internal Medicine. 38. 309-314 (1999)
[文献書誌] Miyata T et al.: ""Carbonyl Stress" and long-term uremic complications"Advanced in Nephrology. (in press). (1999)
[文献書誌] Wada T et al.: "β2-microglobulin and renal bone disease"Perit Dial Int. 10[Supple 2]. 424-427 (1999)
[文献書誌] Izuhara Y et al.: "A sensitive and specific ELISA for plasma pentosidine"Nephrol Dial Transplant. 14. 576-580 (1999)
[文献書誌] Suzuki D et al.: "Immunohistochemical evdence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions"J Am Soc Nephrol. 10. 822-832 (1999)
[文献書誌] Jadoul M et. al: "Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress""Kidney Int. 55. 2487-2492 (1999)
[文献書誌] Miyata T et al.: "Increased carbonyl modification of proteins by autoxidation products of carbohydrates and lipids in uremia"Int J Art Org. 22. 195-198 (1999)
[文献書誌] Miyata T et al.: "Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney"J Am Soc Nephrol. 10. 1590-1595 (1999)
[文献書誌] Miyata T et al.: ""Carbonyl stress" and dialysis-related amyloidosis"Nephrol Dial Transplant. (in press).
[文献書誌] 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).
[文献書誌] Liu W, et al.: "4-Hydroxynonenal induces Fas-independent redox-related activation of caspase-3"J Cell Sci. (in press).
[文献書誌] Miyata T et al.: "Relevance of carbonyl and oxidative stress in long-term complications in hemodialysis"Kidney Int. (in press).
[文献書誌] Miyata T et al.: "Alterations in nonenzymatic biochemistry of carbohydrates and lipids in uremia"Massry and Glassock's Text book of Nephrology. (in press).
[文献書誌] Miyata T et al.: "Adovanced glycation and oxidation end products"J Am Soc Nephrol. (in press).
[文献書誌] 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).
[文献書誌] 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).
[文献書誌] 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).
[文献書誌] Hori Y et al.: "A complement regulatory protein, modulates renal interstitial disease induced by proteinuria in rats"Kidney Int. (in press).
[文献書誌] Miyata T et. al: "Redox Regulation of Cell Signaling and Its Clinical Application."Oxdative stress-induced"Carbonylstress"in uremia. 10 (1999)

1999 年度 実績報告書

メサンギウム細胞特異発現遺伝子群の機能解析及びその病因論に関する研究

研究代表者

黒川 清 東海大学, 医学部, 教授 (30167390)

研究成果

[文献書誌] Ahkand AA et al.: "Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase p60_<c-src>"J Cellular Biochemistry. 72. 1-7 (1999)

[文献書誌] Miyata T et al.: "Alterations in non-enzymatic biochemistry in uremia : Origin and significance of "carbonyl stress"in long-term uremic complications"Kidney Int. 55. 389-399 (1999)

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

[文献書誌] Wada T et al.: "Implication of Carbonyl stress in long-term uremic complications"Nephrol Sial Transplant. Supple 1. 79-81 (1999)

[文献書誌] 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 glycoxidation and lipoxidation reactions in vascular tissue damage"FEBS letter. 445. 202-206 (1999)

[文献書誌] Miyata T et al.: "Carbonyl stress : Increased carbonyl modification of tissue and cellular proteins in uremi"Perit Dial Int. 19[Supple 2]. 58-61 (1999)

[文献書誌] Stein G et. al: "Decrease in serum pentosidine levels of ESRD patients during polysulfone hemodialysis"Nephrol Dial Transplant. 14. 1606-1608 (1999)

[文献書誌] Liu W et al.: "4-Hydroxynonenal triggers an epidermal growth factor receptorlinked signal pathway for growth inhibition"J Cel Sci. 112. 2409-2407 (1999)

[文献書誌] Kawada N et al.: "Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction"Kidney Int. 56. 1004-1013 (1999)

[文献書誌] Nangaku M et al.: "Possible involvement of "carbonyl stress"in the pathogenesis of dialysis-related amyloidosis"Am J Med Sci. 317. 410-415 (1999)

[文献書誌] Suzuki D et al.: "Carbonyl stress and diabetic nephropathy"Internal Medicine. 38. 309-314 (1999)

[文献書誌] Miyata T et al.: ""Carbonyl Stress" and long-term uremic complications"Advanced in Nephrology. (in press). (1999)

[文献書誌] Wada T et al.: "β2-microglobulin and renal bone disease"Perit Dial Int. 10[Supple 2]. 424-427 (1999)

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

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

[文献書誌] Jadoul M et. al: "Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress""Kidney Int. 55. 2487-2492 (1999)

[文献書誌] Miyata T et al.: "Increased carbonyl modification of proteins by autoxidation products of carbohydrates and lipids in uremia"Int J Art Org. 22. 195-198 (1999)

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

[文献書誌] Miyata T et al.: ""Carbonyl stress" and dialysis-related amyloidosis"Nephrol Dial Transplant. (in press).

[文献書誌] 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).

[文献書誌] Liu W, et al.: "4-Hydroxynonenal induces Fas-independent redox-related activation of caspase-3"J Cell Sci. (in press).

[文献書誌] Miyata T et al.: "Relevance of carbonyl and oxidative stress in long-term complications in hemodialysis"Kidney Int. (in press).

[文献書誌] Miyata T et al.: "Alterations in nonenzymatic biochemistry of carbohydrates and lipids in uremia"Massry and Glassock's Text book of Nephrology. (in press).

[文献書誌] Miyata T et al.: "Adovanced glycation and oxidation end products"J Am Soc Nephrol. (in press).

[文献書誌] 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).

[文献書誌] 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).

[文献書誌] 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).

[文献書誌] Hori Y et al.: "A complement regulatory protein, modulates renal interstitial disease induced by proteinuria in rats"Kidney Int. (in press).

[文献書誌] Miyata T et. al: "Redox Regulation of Cell Signaling and Its Clinical Application."Oxdative stress-induced"Carbonylstress"in uremia. 10 (1999)

1999 年度実績報告書

黒川清東海大学, 医学部, 教授 (30167390)