Control of collagen production by human diploid lung fibroblasts

The fibroblast is a differentiated mesenchymal cell which produces and exports collagen, a macromolecule that plays a critical structural role in the function of most organs. To evaluate the control soft tissue fibroblasts have over collagen production, HFL-1, a diploid human lung cell strain, was studied during periods of rapid cell growth and relatively slow growth over 25 population doublings. To minimize environmental influences, the extracellular milieu of the cells was kept constant throughout the study period. Rates of collagen production per cell per unit time were quantitated by labeling HFL-1 with [14C]proline and measuring the production of [14C]hydroxyproline after taking into consideration the specific activity of [14C]proline within the free intracelllular proline pool and the per cent hydroxylation of proline residues in newly synthesized collagen. Although the specific activity of intracellular free proline and the per cent hydroxylation of proline in collagen varied considerably depending on the growth rates of the cells, collagen production by HFL-1 was constant, even during periods of rapid cell growth. Thus, under conditions of a stable environment, populations of soft tissue fibroblasts rigidly control their collagen production. In cultures that maintained a constant doubling time, this stability was maintained over at least 25 population doublings, suggesting that on the average, collagen production appears to be tightly controlled and dissociated from the events and sequelae of cell division.