The age-dependent proliferation of rat aortic smooth muscle cells is independent of differential splicing of PDGF A-chain mRNA.

Overview

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.