マトリックス金属タンパク質酵素は,ペリセルラーフィブリノリシンとして作用することで,新血管化を調節する
1Department of Internal Medicine and University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
Cell
|November 14, 1998
まとめ
内皮細胞は,プラズミノゲン活性化剤ではなく,マトリックス金属タンパク質酵素 (MMP) を使用して,新しい血管形成 (血管新生) 過程で繊維素の障壁を分解します. 膜結合型MMPは,このプロセスの鍵です.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- 生理学 生理学とは
背景:
- 血管新生は,線維素マトリックスを通して内皮細胞の侵入を伴う.
- この侵入を誘発するタンパク質分解のメカニズムは,以前は定義されていなかった.
- この過程におけるプラズミノゲン活性化剤 (PA) - プラズミノゲンシステムの役割は不明であった.
研究 の 目的:
- 血管新生中に内皮細胞が繊維素の障壁を通過するために使用するタンパク質分解機構を解明する.
- このプロセスにおけるPA-プラズミノゲン系とマトリックス金属タンパク質酵素 (MMPs) の役割を決定する.
主な方法:
- PAとプラズミノゲン不足のマウス組織を使用した.
- フィブリンゲルの評価された新血管化 in vitroおよびin vivo.
- 膜型-1 MMP (MT1-MMP) を含む,マトリックスメタロプロテインゼによる内皮細胞の遺伝子トランスフェクションを使用した.
主要な成果:
- 新血管化はPAまたはプラズミノゲン欠乏組織で効果的に発生し,これらのシステムが不要であることを示しています.
- 内皮細胞に由来するMMPは,血管新生中のフィブリンバリアの貫通に不可欠です.
- 膜に結合したMT1-MMPによる感染は,以前無能だった細胞への侵入を回復させた.
- トランスメブランに欠けていたが活発なMT1-MMP変異体は侵入を回復できず,膜局所化の重要性を強調した.
結論:
- 血管新生に不可欠な新しい,PA-独立のフィブリノリチス経路を特定しました.
- 膜に結合したMMPs,特にMT1-MMPは,周細胞性フィブリノリシンとして作用することを実証した.
- MMPsは,新血管化の際にフィブリンを通じた内皮細胞の侵入の重要な調節体として確立されています.
関連する概念動画
Mechanism of Angiogenesis
6.4K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.4K
Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Role of Matrix Metalloproteases in Degradation of ECM
2.9K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.9K
Overview of Cell-Matrix Interactions
8.0K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
8.0K
Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
Clot Retraction and Fibrinolysis
6.0K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
6.0K


