Majesky M W, Benditt E P, Schwartz S M
Department of Pathology, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1988 Mar;85(5):1524-8. doi: 10.1073/pnas.85.5.1524.
Cultured arterial smooth muscle cells (SMC) can produce platelet-derived growth factor (PDGF)-like molecules. This property raises the possibility that SMC-derived PDGFs function as autocrine/paracrine regulators in the formation and maintenance of the artery wall. In this study we have asked if levels of mRNAs directing synthesis of PDGF are modulated in aortic SMC during postnatal development. We report here that genes encoding PDGF A- and B-chain precursors are expressed at similar low levels in intact aortas from newborn and adult rats. Marked differences in regulation of transcript abundance of these genes were revealed when aortic SMC were grown in cell culture. PDGF B-chain transcripts accumulated in passaged newborn rat SMC but not adult rat SMC, whereas PDGF A-chain RNA was found in comparable amounts in SMC from both age groups. Similarly, SMC from newborn rats secreted at least 60-fold more PDGF-like activity into conditioned medium than did adult rat SMC. PDGF B-chain transcripts in newborn rat aortic SMC are short-lived and increased 5-fold by 3 hr after treatment with cycloheximide. In contrast, PDGF A-chain transcripts are more stable, and their constitutive levels were generally unaffected by cycloheximide. These results show that PDGF A- and B-chain genes are transcribed in the normal rat aorta and provide evidence for age-related change in the control of PDGF B-chain gene expression in aortic SMC. Independent regulation of transcript levels in cultured SMC leaves open the possibility that PDGFs of different composition (AA, AB, BB) play different roles in normal function of the artery wall.
培养的动脉平滑肌细胞（SMC）能够产生血小板衍生生长因子（PDGF）样分子。这一特性增加了一种可能性，即SMC衍生的PDGF作为自分泌/旁分泌调节因子参与动脉壁的形成和维持。在本研究中，我们探讨了在出生后发育过程中，主动脉SMC中指导PDGF合成的mRNA水平是否受到调节。我们在此报告，编码PDGF A链和B链前体的基因在新生大鼠和成年大鼠的完整主动脉中以相似的低水平表达。当主动脉SMC在细胞培养中生长时，发现这些基因转录本丰度的调节存在显著差异。PDGF B链转录本在传代的新生大鼠SMC中积累，而成年大鼠SMC中则没有，而两个年龄组的SMC中PDGF A链RNA的含量相当。同样，新生大鼠的SMC向条件培养基中分泌的PDGF样活性比成年大鼠的SMC至少高60倍。新生大鼠主动脉SMC中的PDGF B链转录本寿命较短，在用环己酰亚胺处理3小时后增加了5倍。相比之下，PDGF A链转录本更稳定，其组成水平通常不受环己酰亚胺的影响。这些结果表明，PDGF A链和B链基因在正常大鼠主动脉中被转录，并为主动脉SMC中PDGF B链基因表达控制的年龄相关变化提供了证据。培养的SMC中转录水平的独立调节使得不同组成（AA、AB、BB）的PDGF在动脉壁正常功能中发挥不同作用成为可能。
