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 develop asbestos-induced fibrogenesis, whereas several other inbred strains rapidly 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) proliferated 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 MLFs compared to those from C57BL/6 mice. Fibroblasts from the SJL mouse strain, from a C57BL/6-129 hybrid, and from the 3T3 cell line all proliferated more vigorously than MLFs from the 129 mice. In addition, the 129 MLFs exhibited reduced expression of alpha1 procollagen mRNA consequent to treatment with tumor necrosisfactor alpha. Based on these new findings, we suggest that the reduced fibrogenesis in asbestos-exposed 129 mice is due to an intrinsic difference in the ability of the lung fibroblasts to respond to peptide growth factors.