Szabo P, Weksler D, Whittington E, Weksler B B
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Mech Ageing Dev. 1993 Feb;67(1-2):79-89. doi: 10.1016/0047-6374(93)90113-6.
Arterial smooth muscle cells (SMC) from old rats proliferate in vivo (after injury) and in vitro more rapidly than smooth muscle cells from young rats. We previously observed that SMC from old rats contained more PDGF-like growth factor activity than did young SMC. We therefore tested the hypothesis that age-related differences in type of PDGF A-chain gene expression might be responsible for the difference in growth factor activity, since PDGF B-chain gene is minimally expressed both in young and old SMC. Specifically we tested if the old SMC predominantly expressed the long form of the A-chain mRNA, leading to autocrine stimulation by cell-associated PDGF AA-homodimers. A partial cDNA for the rat PDGF A-chain was cloned and sequenced; it is highly conserved compared to the human PDGF-A chain and similarly has two forms, a long form containing all exons, which tends to remain cell-associated and a short form lacking exon 6, which tends to be secreted. Different tissues of both young and old animals express different ratios of these two forms of PDGF-A. However, the relative expression of the different mRNA forms does not change with age, suggesting that differential splicing of PDGF-A and accumulation of cell-associated PDGF A-chain does not determine the enhanced growth potential of old rat SMC.
老年大鼠的动脉平滑肌细胞（SMC）在体内（损伤后）和体外的增殖速度均比幼年大鼠的平滑肌细胞更快。我们之前观察到，老年大鼠的SMC比幼年SMC含有更多的血小板源性生长因子（PDGF）样生长因子活性。因此，我们检验了这样一个假设：由于PDGF B链基因在幼年和老年SMC中表达极少，PDGF A链基因表达类型的年龄相关差异可能是生长因子活性差异的原因。具体而言，我们检验了老年SMC是否主要表达A链mRNA的长形式，从而导致细胞相关的PDGF AA同二聚体产生自分泌刺激。克隆并测序了大鼠PDGF A链的部分cDNA；与人类PDGF - A链相比，它高度保守，同样有两种形式，一种长形式包含所有外显子，倾向于与细胞相关，另一种短形式缺少外显子6，倾向于被分泌。幼年和老年动物的不同组织表达这两种形式的PDGF - A的比例不同。然而，不同mRNA形式的相对表达不会随年龄变化，这表明PDGF - A的可变剪接和细胞相关PDGF A链的积累并不能决定老年大鼠SMC增强的生长潜力。
