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パーレカン (perlecan),ベースラミナプロテオグリカン (basal lamina proteoglycan) は,基礎線維細胞成長因子-受容体結合,ミトゲネシス,および血管新生を促進する

D Aviezer¹, D Hecht, M Safran

¹Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.

|December 16, 1994

まとめ

基礎膜のプロテオグリカンであるペルレカンは,線維細胞成長因子 (FGF) 受容体結合と活性を強化します. また,生体内でFGF媒介の血管形成を強力に誘導する.

科学分野:

バイオケミストリーバイオケミストリー
細胞生物学細胞生物学
細胞外マトリックス研究

背景:

ヘパラン硫酸プロテオグリカン (HSPG) は,成長因子シグナル伝達の重要なレギュレータです.
線維芽生殖成長因子 (FGF) の活性を媒介する特定のHSPGの役割については,さらなる解明が必要である.

研究の目的:

基礎線維芽生殖成長因子 (bFGF) 受容体結合と生物学的活動を促進する細胞タンパク質グリカンを特定する.
bFGFの付属受容体および血管新生調節剤としてのペルレカンの可能性を調査する.

主な方法:

様々なヘパラン硫酸プロテオグリカン (HSPG) のアフィニティ浄化.
bFGF受容体結合とミトゲン活性に対する測定.
ウサギの耳を使ったインビヴォ血管新生モデル.

主要な成果:

ペルレカンは,大きな基礎膜HSPGであり,bFGFがHS欠乏細胞と溶解性FGF受容体との高親和結合を誘導した.
ペルレカンは,bFGF.のヘパリン依存のミトジェニック活性を著しく増加させた.
ペルレカンに対するモノクローナル抗体は,受容体結合促進活性を中和した.
ペルレカンは,ウサギの耳の血管新生モデルでbFGF媒介の新血管化の強力な誘導を示した.

結論:

ペルレカンは,bFGFの低親和性付属受容体として機能する.
ペルレカンは,bFGF媒介の新血管化に影響を与える主要な血管新生調節剤として特定されています.

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