Kletsas D, Stathakos D, Sorrentino V, Philipson L
Institute of Biology, N.C.S.R. Demokritos, Athens, Greece.
Exp Cell Res. 1995 Apr;217(2):477-83. doi: 10.1006/excr.1995.1112.
Transforming growth factor-beta (TGF-beta) inhibits DNA synthesis in dense cultures of young human embryonic fibroblasts and antagonizes the mitogenic action of platelet-derived growth factor (PDGF). The inhibition of the PDGF-BB action by TGF-beta was independent of the induction of mRNAs for the PDGF-A chain and PDGF-beta receptor, the predominant types of PDGF receptor in human fibroblasts. The TGF-beta-mediated inhibition did not influence the expression of various genes that are involved in the transition from the arrested (GO) state to the S phase of the cell cycle. Indeed, TGF-beta upregulated the "early" genes c-myc, c-fos, and junB and downregulated the growth arrest-specific (gas) genes. These results suggest that the inhibition of DNA synthesis by TGF-beta in human fibroblasts is independent of modulation of expression of early and gas genes, placing the TGF-beta block comparatively late in the GO to S transition. In cultures of senescent human fibroblasts TGF-beta stimulated DNA synthesis but, nevertheless, had the same effect as in young cells on the expression of PDGF chains and receptor genes, as well as on early and gas genes, with the exception of a significantly lower induction of c-fos.
转化生长因子-β（TGF-β）可抑制年轻人类胚胎成纤维细胞密集培养物中的DNA合成，并拮抗血小板衍生生长因子（PDGF）的促有丝分裂作用。TGF-β对PDGF-BB作用的抑制与人类成纤维细胞中主要类型的PDGF受体即PDGF-A链和PDGF-β受体的mRNA诱导无关。TGF-β介导的抑制作用并不影响参与细胞周期从静止（G0）状态过渡到S期的各种基因的表达。实际上，TGF-β上调了“早期”基因c-myc、c-fos和junB，并下调了生长停滞特异性（gas）基因。这些结果表明，TGF-β对人类成纤维细胞中DNA合成的抑制与早期基因和gas基因表达的调节无关，这使得TGF-β的阻断作用在G0到S转变过程中相对较晚。在衰老的人类成纤维细胞培养物中，TGF-β刺激了DNA合成，但尽管如此，它对PDGF链和受体基因以及早期基因和gas基因表达的影响与在年轻细胞中相同，只是c-fos的诱导明显较低。
