van Wieringen Tijs, Kimani Stanley G, Hultgård-Ekwall Anna-Karin, Forsberg Jens, Reyhani Vahid, Engström Ake, Rubin Kristofer
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Uppsala, Sweden.
Exp Cell Res. 2009 Jun 10;315(10):1745-58. doi: 10.1016/j.yexcr.2009.02.005. Epub 2009 Feb 20.
Prostaglandin E(1) (PGE(1)) lowers dermal interstitial fluid pressure (IFP) in vivo and inhibits fibroblast-mediated collagen gel contraction in vitro. PDGF-BB, in contrast, stimulates contraction and normalizes IFP lowered as a result of anaphylaxis. Human diploid AG1518 fibroblasts expressed EP2, EP3 and IP prostaglandin receptors. The inhibitory effect of PGE(1) on contraction depended on cAMP. Short-term stimulation with PDGF-BB transiently induced formation of actin-containing membrane and circular ruffles and breakdown of stress fibers. PGE(1) had no effect on stress fibers nor did it modulate the effects of PDGF-BB. PGE(1) alone or in combination with PDGF-BB inhibited initial adhesion and spreading to collagen. PDGF-BB had no effect on adhesion but stimulated cell spreading. Two-dimensional gel electrophoresis and MALDI TOF analyses of SDS/Triton X-100-soluble proteins revealed changes in migration pattern of actin-binding proteins. Interestingly, PDGF-BB and PGE(1) affected both similar and different sets of actin-binding proteins. PDGF-BB and PGE(1) did not trans-modulate their respective effects on actin-binding proteins, cytoskeletal organization or initial adhesion. Our data show that PDGF-BB stimulates actin cytoskeleton dynamics, whereas PGE(1) inhibits processes dependent on cytoskeletal motor functions. We suggest that these different activities may partly explain the contrasting effects of PGE(1) and PDGF-BB on contraction and IFP.
前列腺素E(1)（PGE(1)）可降低体内真皮间质液压力（IFP），并在体外抑制成纤维细胞介导的胶原凝胶收缩。相比之下，血小板衍生生长因子BB（PDGF-BB）可刺激收缩，并使因过敏反应而降低的IFP恢复正常。人二倍体AG1518成纤维细胞表达EP2、EP3和IP前列腺素受体。PGE(1)对收缩的抑制作用取决于环磷酸腺苷（cAMP）。用PDGF-BB进行短期刺激可短暂诱导含肌动蛋白的膜和环形褶皱的形成以及应力纤维的分解。PGE(1)对应力纤维无影响，也不调节PDGF-BB的作用。单独使用PGE(1)或与PDGF-BB联合使用均可抑制细胞与胶原蛋白的初始黏附及铺展。PDGF-BB对黏附无影响，但可刺激细胞铺展。对SDS/Triton X-100可溶性蛋白进行二维凝胶电泳和基质辅助激光解吸电离飞行时间（MALDI TOF）分析，发现肌动蛋白结合蛋白的迁移模式发生了变化。有趣的是，PDGF-BB和PGE(1)对肌动蛋白结合蛋白的影响既有相似之处，也有不同之处。PDGF-BB和PGE(1)不会相互调节它们对肌动蛋白结合蛋白、细胞骨架组织或初始黏附的各自影响。我们的数据表明，PDGF-BB可刺激肌动蛋白细胞骨架动力学，而PGE(1)可抑制依赖于细胞骨架运动功能的过程。我们认为，这些不同的活性可能部分解释了PGE(1)和PDGF-BB对收缩和IFP产生的相反作用。
