SPARC (SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE) REGULATES ENDOTHELIAL-CELL SHAPE AND BARRIER FUNCTION
SPARC (SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE) REGULATES ENDOTHELIAL-CELL SHAPE AND BARRIER FUNCTION
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DOI：
10.1073/pnas.91.8.3448
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
SAGE, EH
中科院分区：
文献类型：
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作者：
GOLDBLUM, SE;DING, XD;SAGE, EH
SPARC(富含半胱氨酸的酸性分泌蛋白)在体外可被内皮细胞选择性地表达，并诱导贴壁内皮细胞发生圆化。为了确定SPARC是否会影响内皮细胞的通透性，我们研究了外源性SPARC对C-14标记的牛血清白蛋白跨融合后的牛肺动脉内皮细胞运动的影响。当浓度大于或等于0.5ug/ml时，SPARC以剂量依赖的方式增加(P<；0.02)经内皮细胞的白蛋白通量。在固定剂量(15ug/ml)下，暴露时间大于或等于1h的白蛋白通量增加(P<；0.005)1.3-3.6倍；这种增加可被抗SPARC抗体阻断，但不能被蛋白质合成的抑制所阻断。屏障功能障碍与细胞活力丧失无关。单层膜在SPARC作用下表现出圆形的形态和细胞间隙。预先用连翘苷稳定F-肌动蛋白可防止SPARC引起的屏障功能改变(P=0.0001)。牛主动脉和视网膜微血管内皮细胞对SPARC也有反应。我们认为，SPARC通过F-肌动蛋白依赖的细胞形状变化来调节内皮屏障的功能，这与细胞间隙的出现是一致的，这为大分子的外渗提供了一条细胞旁途径。
SPARC (secreted protein acidic and rich in cysteine) can be selectively expressed by the endothelium in response to certain types of injury and induces rounding in adherent endothelial cells in vitro. To determine whether SPARC might influence endothelial permeability, we studied the effect of exogenous SPARC on the movement of C-14-labeled bovine serum albumin across postconfluent bovine pulmonary artery endothelial cells. SPARC increased (P < 0.02) transendothelial albumin flux in a dose-dependent manner at concentrations greater-than-or-equal-to 0.5 mug/ml. At a fixed dose (15 mug/ml), exposure times greater-than-or-equal-to 1 h augmented (P < 0.005) albumin flux by 1.3- to 3.6-fold; this increase was blocked by anti-SPARC antibodies but not by inhibition of protein synthesis. Barrier dysfunction was not associated with loss of cell' viability. Monolayers exposed to SPARC exhibited a rounded morphology and intercellular gaps. Prior stabilization of F-actin with phallicidin protected against the changes in barrier function (P = 0.0001) that were otherwise induced by SPARC. Bovine aortic and retinal microvascular endothelia also responded to SPARC. We propose that SPARC regulates endothelial barrier function through F-actin-dependent changes in cell shape, coincident with the appearance of intercellular gaps, that provide a paracellular pathway for extravasation of macromolecules.