整合素αvβ3-RGDS位点相互作用介导纤维蛋白所致的肾小球内皮细胞表型变化

INTEGRIN v3RGDS INTERACTION MEDIATES PHENOTYPE CHANGES OF GLOMERULAR ENDOTHELIAL CELLS INDUCED BY FIBRIN

观察了体外培养的人类肾小球内皮细胞（ＧＥＣ）在纤维蛋白凝胶上的生长状态，以及在ＧＥＣ表面覆盖纤维蛋白凝胶对ＧＥＣ表型的影响，并进行了干预试验。结果发现，ＧＥＣ在纤维蛋白凝胶包被的细胞培养板上培养可以自发地形成典型的血管样结构。αｖβ３整合素单抗２３Ｃ６可以显著促进纤维蛋白介导的血管样结构的形成，而精氨酰－甘氨酰－天门冬氨酰－丝氨酸（ＲＧＤＳ）四肽、放线菌酮、放线菌素Ｄ对血管样结构的形成具有抑制作用（Ｐ＜０．００１）。在融合态ＧＥＣ细胞单层表面原位形成ｄｅｓ－ＡＡ－纤维蛋白或ｄｅｓ－ＡＡＢＢ－纤维蛋白凝胶均可引起ＧＥＣ单层结构破坏，肝素、放线菌酮、放线菌素Ｄ、非免疫小鼠ＩｇＧ以及精氨酰－甘氨酰－甘氨酰－丝氨酸（ＲＧＧＳ）四肽不能阻断纤维蛋白诱导的ＧＥＣ单层结构破坏，而２３Ｃ６、ＲＧＤＳ四肽可以完全阻断上述改变。说明αｖβ３整合素－ＲＧＤＳ位点相互作用介导了纤维蛋白所致ＧＥＣ单层结构破坏和血管样结构形成，ＲＧＤＳ四肽防治纤维蛋白所诱发的ＧＥＣ表型变化可能具有潜在的价值。

In vitro studies were carried out to observe the growing status of human glomerular endothelial cells (GECs) stimulated by covering and underlying fibrin gels in the presence or absence of antiv3 integrin monoclonal antibody 23C6,synthetic RGDS peptide, heparin, cycloheximide, and actinomycin D, respectively. Results: GECs developed capillary tube structure on fibrin gel, which was promoted by 23C6, but inhibited by RGDS peptide, cycloheximide, and actinomycin D (P<0.001). Similar and specific disorganization of GEC monolayers was induced by covering them with desAAfibrin and desAABBfibrin , and this phenomenon was prevented by antiv3 integrin 23C6 and synthetic RGDS peptide , while nonimmune mouse IgG, synthetic RGGS peptide, cycloheximide, and actinomycin D had no similar effects. It is concluded that GECs cultured on fibrin gels may develop capillary tube structure spontaneously and that GECs covered by fibrin gels may undergo disorganization. These GEC phenotype changes are probably both mediate