INDUCTION OF SUBCUTANEOUS TISSUE FIBROSIS IN NEWBORN MICE BY TRANSFORMING-GROWTH-FACTOR BETA-SIMULTANEOUS APPLICATION WITH BASIC FIBROBLASTGROWTH-FACTOR CAUSES PERSISTENT FIBROSIS (VOL 237, PG 292, 1997)

To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta 1, b eta 2, and beta 3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The chan ges after 3 days of injection were more pronounced in the tissue injec ted with TGF-beta 2 or beta 3 than that with TGF-beta 1. In situ hybri dization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta inje ction, which suggested that fibroblasts were activated by TGF-beta. Ne xt, me investigated the cooperative effects of TGF-beta and other grow th factors including basic fibroblast growth factor (bFGF). The simult aneous application of TGF-beta and bFGF caused apparent tissue fibrosi s which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in est ablishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal model mill be useful for f uture studies in this area. (C) 1997 Academic Press.