PLATELET-DERIVED GROWTH-FACTOR REGULATES ACTIN ISOFORM EXPRESSION AND GROWTH-STATE IN CULTURED RAT AORTIC SMOOTH-MUSCLE CELLS
PLATELET-DERIVED GROWTH-FACTOR REGULATES ACTIN ISOFORM EXPRESSION AND GROWTH-STATE IN CULTURED RAT AORTIC SMOOTH-MUSCLE CELLS
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DOI：
10.1002/jcp.1041420325
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发表时间：
1990-03-01
影响因子：
5.6
通讯作者：
OWENS, GK
中科院分区：
文献类型：
--
作者：
BLANK, RS;OWENS, GK
通过观察血小板源性生长因子（PDGF）对培养大鼠主动脉平滑肌细胞（SMC）特异性收缩蛋白SM α -肌动蛋白表达的影响，探讨PDGF在体外控制平滑肌细胞（SMC）分化中的作用。静止的、融合后的SMC表达最高水平的α -肌动蛋白，并通过进入细胞周期和经历大约一个同步的DNA合成来响应人血小板来源的生长因子（部分从血小板中纯化）。同时，这些培养表现出α -肌动蛋白合成的显著减少。PDGF慢性治疗（间隔8或12小时72小时）与胸苷标记指数的短暂升高和α -肌动蛋白表达的降低相关。有趣的是，在初始治疗后48至72小时，胸苷标记指数恢复到接近控制水平，而SM α肌动蛋白的表达仍然下降。这种效应是可逆的；去除PDGF后，α -肌动蛋白合成立即增加。当随后用10%胎牛血清（FBS）刺激时，经PDGF慢性预处理的细胞比经PDGF载体预处理的细胞早大约4小时进入S期，这与慢性PDGF处理对SMC中α -肌动蛋白合成的持续抑制与部分细胞周期传递有关的观点一致。用高纯度重组PDGF-BB进行慢性治疗，对α -肌动蛋白合成和部分细胞周期运输产生类似的影响。流式细胞术分析显示，慢性pdgf处理的SMC前角光散射增加了25%，这是细胞大小的指标。这些数据暗示了PDGF在SMC分化调控中的可能作用，并表明该有丝分裂原在伴随SMC生长的表型调节和与细胞周期进展相关的细胞肥大的介导中可能发挥重要作用。
The role of platelet-derived growth factor (PDGF) in the control of smooth muscle cell (SMC) differentiation was explored in vitro by examining its effects on expression of the smooth muscle (SM) specific contractile protein SM alpha actin in cultured rat aortic SMC. Quiescent, postconfluent SMC express maximal levels of alpha actin and responded to human platelet-derived growth factor (partially purified from platelets) by entering the cell cycle and undergoing approximately one synchronous round of DNA synthesis. Concomitantly, these cultures exhibited a marked reduction in alpha actin synthesis. Chronic treatment with PDGF (72 hours at 8 or 12 hour intervals) was associated with a transient increase in thymidine labeling index and a decrease in alpha actin expression. Interestingly, between 48 and 72 hours following initial treatment, thymidine labeling indices returned to near control levels while SM alpha actin expression remained depressed. This effect was reversible; fractional alpha actin synthesis increased immediately after PDGF removal. When subsequently stimulated with 10% fetal bovine serum (FBS), cells chronically pretreated with PDGF entered S phase approximately 4 hours earlier than cells pretreated with PDGF vehicle, consistent with the idea that the maintained suppression of alpha actin synthesis in SMC subjected to chronic PDGF treatment was associated with partial cell cycle transit. Chronic treatment with highly purified recombinant PDGF-BB elicited similar effects on alpha actin synthesis and partial cell cycle transit. Flow cytometric analysis of chronic PDGF-treated SMC demonstrated a 25% increase in forward angle light scatter, an index of cell size. These data implicate a possible role for PDGF in regulation of SMC differentiation and suggests a potentially important role for this mitogen in the phenotypic modulation accompanying SMC growth and in mediation of cellular hypertrophy associated with cell cycle progession.