Tsukamoto T, Matsui T, Takaishi T, Ito M, Fukase M, Chihara K
Department of Medicine, Kobe University School of Medicine, Japan.
Cell Growth Differ. 1994 Feb;5(2):207-12.
Retinoic acid (RA) plays an important role in the control of cell growth and differentiation. To elucidate the effects of RA for osteoblasts, we examined here the responsiveness of normal osteoblast-like MC3T3-E1 cells treated with RA for two growth factors, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). The transcripts of alpha- and gamma-RA receptors were constitutively expressed in MC3T3-E1 cells, and the expression of the beta-RA receptor mRNA was induced by RA. The PDGF-induced mitogenicity of MC3T3-E1 cells was significantly enhanced by 1 microM RA pretreatment, whereas the EGF-induced mitogenicity was suppressed by the same treatment. The expression of both alpha- and beta-PDGF receptor gene products detected by RNA blot and immunoblot analyses was significantly increased by RA. The increased expression of PDGF receptors was accompanied by the augmentation of PDGF-induced receptor autophosphorylation following the enhancement of inositol phosphate hydrolysis. In contrast, EGF-induced receptor autophosphorylation was suppressed in RA-treated cells, whereas the expression level of EGF receptor was not affected. These findings demonstrate that RA could control the cell growth of osteoblast-like MC3T3-E1 cells not only by regulating the gene expression of growth factor receptors, but also by modulating the ligand-induced receptor autophosphorylation.
维甲酸（RA）在细胞生长和分化的调控中发挥着重要作用。为了阐明RA对成骨细胞的影响，我们在此检测了用RA处理的正常成骨样MC3T3-E1细胞对两种生长因子，即血小板衍生生长因子（PDGF）和表皮生长因子（EGF）的反应性。α-和γ-RA受体的转录本在MC3T3-E1细胞中组成性表达，β-RA受体mRNA的表达由RA诱导。1μM RA预处理显著增强了MC3T3-E1细胞的PDGF诱导的有丝分裂活性，而相同处理则抑制了EGF诱导的有丝分裂活性。通过RNA印迹和免疫印迹分析检测到的α-和β-PDGF受体基因产物的表达均因RA而显著增加。PDGF受体表达的增加伴随着磷酸肌醇水解增强后PDGF诱导的受体自身磷酸化的增强。相反，在RA处理的细胞中，EGF诱导的受体自身磷酸化受到抑制，而EGF受体的表达水平不受影响。这些发现表明，RA不仅可以通过调节生长因子受体的基因表达，还可以通过调节配体诱导的受体自身磷酸化来控制成骨样MC3T3-E1细胞的生长。
