Dynamic Changes in the Functional Characteristics of the Interstitial Fibroblast During Lung Repair

Abstract

To evaluate the mechanisms involved in the regulation of fibroblast function during the repair of fibrotic lung injury, we isolated lung fibroblasts from adult male Fischer-344 rats before the induction of severe unilateral paraquat lung injury, as well as 1 and 14 days later. Fibroblasts were utilized at an early generation time to avoid senescence. In general, fibroblasts of injured lungs displayed significant increases in proliferative and matrix synthesis properties, with more pronounced increases detected early after the induction of injury. This was true ofDNA synthesis, which increased by 3- and 1.4-fold on days 1 and 14, respectively; tyrosine kinase activity, which increased by 4-and 3.5-fold; fibronectin synthesis, 14- and 8-fold, respectively; and glycosaminoglycans synthesis, 4.4- and 3 fold, respectively. The increase in function of fibroblasts isolated from the immediate influence of extrinsic growth factors suggests that fibroblast function during repair may be under intrinsic as well as extrinsic control. In the early phases of repair, intrinsic changes may be more dominant and may result in autoregulation of fibroblast function. In the later phases of repair, despite some reduction in intrinsic fibroblast activation, exposure to extrinsic growth factors may result in maintaining the state of activation and in sustaining the repair process.