Potential role of pyrroline 5-carboxylate in regulation of collagen biosynthesis in cultured human skin fibroblasts

Although insulin-like growth factor-I (IGF-I) is known as an important stim ulator of collagen biosynthesis in collagen-producing cells, the mechanism and endpoints by which it regulate the process remain largely unknown. Seru m of acutely fasted rats contained reduced amount of IGF-I (72 +/- 16 ng/ml ) and showed about 75% reduced ability to stimulate collagen and DNA synthe sis in confluent human skin fibroblasts in comparison to the effect of cont rol rat serum (IGF-I, 168 +/- 19 ng/ml). An addition of IGF-I (at least 40 ng/ml) to fasted rat serum restored its mitogenic activity but could not re store its ability to stimulate collagen biosynthesis to control values duri ng 24 h of incubation. However, when the cells were incubated in fasted rat serum supplemented with 40 ng/ml of IGF-I for 48 h, collagen biosynthesis was restored to control values. It suggests that the stimulatory role of IG F-I in collagen biosynthesis undergo indirectly. We considered pyrroline-5- carboxylate (P5C) as a candidate to play a direct role in this process. Sin ce IGF-I and P5C are known to be decreased in serum of fasted rats it seems that the action of IGF-I on collagen biosynthesis may involve participatio n of P5C. We have found that serum of fasted rats (showing low level of P5C ) supplemented with 1 mmol/l P5C induced collagen biosynthesis in confluent human skin fibroblasts during 24 h to control values. Supporting evidence comes from the experiment showing stimulatory action of P5C on collagen bio synthesis in fibroblasts cultured in serum-free medium. Our results postula te potential role of P5C in regulation of collagen biosynthesis and indicat e participation of this molecule in the pathway of IGF-I action in this pro cess. (C) 2000 Elsevier Science Inc. All rights reserved.