Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro

Lung fibroblasts are activated to Proliferate and produce connective tissue during the development of lung fibrosis. The 129 mouse strain does not dev elop abestos-induced fibrogenesis, whereas several other inbred strains rap idly respond to inhaled fibers. Thus, in the experiments presented here, we have compared the responses of Primary lung fibroblasts isolated from 129 and C57BL/6 mice. The 129 and C57BL/6 mouse lung fibroblasts (MLFs) prolife rated similarly in 10% fetal bovine serum (FBS), but after quiescence, the 129 MLFs grew more slowly in serum and responded less to the BB isoform of platelet-derived growth factor This is consistent with our finding that the mRNA for the PDGF a receptor exhibits reduced expression by the 129 III-l' s compared to those front C57BL/6 mice. Fibroblasts from the SJL mouse stra in, from a C57BL/6-129 hybrid, and from the 3T3 cell line all proliferated more vigorously than MLFs front the 129 mice. In addition, the 129 MLFs exh ibited reduced expression of alpha1 procollagen mRNA consequent to treatmen t with tumor necrosis factor alpha. Based on these new findings, we suggest that the reduced fibrogenesis tit asbestos-exposed 129 mice is due to an i ntrinsic difference in the ability of the lung fibroblasts to respond to pe ptide growth factors.