DECREASED LEVELS OF ALPHA-1(I) PROCOLLAGEN MESSENGER-RNA IN DERMAL FIBROBLASTS GROWN ON FIBRIN GELS AND IN RESPONSE TO FIBRINOPEPTIDE-B

We have investigated human neonatal fibroblast synthetic activity in r esponse to fibrin substrates and components of fibrin formation and de gradation. Greater than threefold downregulation of procollagen mRNA l evels was seen 24 hours after fibroblasts were grown on fibrin gels as compared to tissue culture plastic. This downregulation occurred in b oth reptilase-generated fibrin (retention of fibrinopeptide B) and thr ombin-generated fibrin (loss of both fibrinopeptide A and B). However, fibroblasts grown on fibrin retained their capacity to respond to the stimulatory action of transforming growth factor (TGF)-beta 1. Fibrob lasts seeded on reptilase-generated fibrin displayed an abnormal morph ology manifested by dendritic appearance and cell rounding, while fibr oblast attachment was enhanced by 30% on thrombin-generated fibrin sub strate (P < 0.02). Fibrinopeptides A and B, which are generated during fibrin formation, increased and decreased procollagen mRNA levels, re spectively. Tissue plasminogen activator (t-PA) increased procollagen mRNA and TCF-beta 1 levels as early as 6 hours after cells were grown on tissue culture plastic, but this stimulation did not occur in cells cultured on a fibrin substrate. We conclude that alpha 1(l) procollag en mRNA levels in cultures of human dermal fibroblasts are consistentl y downregulated by a fibrin substrate and are directly and profoundly influenced by complex interactions between components involved in the formation and removal of fibrin. (C) 1995 Wiley-Liss, Inc.