AbstractWe tested the hypothesis that normal synovial fibroblasts might proliferate in response to transforming growth factors (TGFs), peptides that are extracted with acid‐ethanol from bovine kidney or salivary gland and that cause anchorage‐independent growth of normal cells. A 72‐hour exposure of confluent monolayers of rabbit synovial fibroblasts in 10 fetal calf serum to partially purified TGF‐β in the presence of TGF‐β gave a 2‐ to 5‐fold increase in incorporation of3H‐thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography‐purified TGF‐β in the presence of epidermal growth factor (EGF) (a type of TGF‐β). By itself, purified TGF‐β was not mitogenic; it depended absolutely on EGF. However, only TGF‐β along with EGF, and not EGF alone, induced a marked morphologic change: a piling up of cells into foci resembling those commonly seen in primary cultures of rheumatoid synovial cells. Mitogenic responses induced by the TGF‐β‐EGF combination were prevented by all‐trans‐retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF‐β, a peptide extracted from normal cells, can act in concert with EGF to cause proliferation and piling up of synovial cells and raise the possibility that these factors may play a role in rheumatoid arthritis and other prol
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