Abstract
A hepatic fibrogenic factor (HFF) isolated from fibrotic rat livers has previously been shown to stimulate the transcription of type I procollagen genes in cultured fibroblasts (Raghow, R., Gossage, D., Seyer, J. M., and Kang, A.H. (1984) J. Biol. Chem. 259, 12718-12723). To test if the expression of other collagen genes was similarly affected by the fibrogenic factor, we measured the rates of types I, III, and V procollagen synthesis in two different cell lines after treatment with HFF. The effect of fibrogenic factor on types I and III procollagens was tested in rat fibroblasts, while a human rhabdomyosarcoma cell line was used to evaluate the effect of HFF on type V procollagen synthesis. Incubation with rat fibroblasts resulted in a 3-4-fold stimulation of the synthesis of both types I and III procollagens in a time-dependent manner. The stimulated rates of types I and III procollagen synthesis accompanied an increase in the steady-state levels of their corresponding mRNAs. When A204 cells, which are derived from a rhabdomyosarcoma and exclusively synthesize type V procollagen, were incubated with the fibrogenic factor, a 3-4-fold stimulation of the synthesis of both pro-alpha 1(V) and pro-alpha 2(V) chains was seen. Using a cDNA probe for pro-alpha 2(V), we also observed that there was a 2-3-fold increase in the steady-state level of pro-alpha 2(V) mRNA in A204 cells after treatment with the fibrogenic factor. In both rat fibroblasts and A204 cells the steady-state levels of beta-actin mRNA were minimally affected by fibrogenic factor, suggesting that the procollagen genes were preferentially affected. Since types I, III, and V collagens are present in the normal liver and accumulate aberrantly in the fibrotic liver, we suggest that fibrogenic factor may play an important role in determining the altered collagen composition of the fibrotic liver. Based on these data, we also speculate that the regulation of the biosynthesis of a variety of procollagens in diverse cell types by HFF possibly occurs by a common mechanism.
Highlights
A hepatic fibrogenic factor (HFF) isolated from fi- toxic, infectious, or immunologic injuries to theliver are just brotic rat livers hapsreviously been showtno stimulate beginning to beelucidated (1-4)
In humans withalcohol-induced were minimally affected by fibrogenicfactor, suggest- cirrhosis there is a n increase in the ratio of type 1:type I11 ing that theprocollagen genes were preferentially affected
Since types I, 111, and V collagens are present in the normal liver and accumulate aberrantly in the fibrotic liver, we suggest that fibrogenic factor may play an important role in determining the alterecdollagen composition of the fibrotic liver.Based on these data, we speculate that theregulation of the biosynthesis of a variety of procollagens in diverse cell collagen as the liver approaches the cirrhotic stage(5, 6)
Summary
Vol 262, No 11, Issue of April 15, pp. 5408-5413,1387 Printed in U.S.A. A Hepatic FibrogenicFactor Stimulates the Synthesiosf Types I, 111, and V Procollagens in CulturedCells*. We examined the effects of HFF on the synthesis of type V procollagen by the A204 cells, a cell that is derived from a human rhabdomyosarcomaand has been documented to exclusively synthesize type V procollagen(23).We quantitated collagen production in these cells after exposure to HFF; their respective mRNAs werequantitated by hybridization to nick-translated cDNA probes specific fotyr pes I11and Vcollagen Based on these studies we conclude that HFFselectively stimulates the synthesis of the three genetically distinct collagens by enhancing the steady state levels of their corresponding mRNAs. Similar to our observations with type I procollagen chains, this stimulation appears to be specific forpro-al(II1) and pro-a2(V) since the steady state levels of P-actin mRNA and totalprotein synthesis were minimally affected
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