title: Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth factor beta require transforming growth factor alpha or epidermal growth factor.
abstract: We 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-beta in the presence of TGF-alpha gave a 2- to 5-fold increase in incorporation of 3H-thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography-purified TGF-beta in the presence of epidermal growth factor (EGF) (a type of TGF-alpha). By itself, purified TGF-beta was not mitogenic; it depended absolutely on EGF. However, only TGF-beta 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-beta-EGF combination were prevented by all-trans-retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF-beta, 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 proliferative but nonmalignant diseases as well.
mesh_terms: D000818:Animals; D002452:Cell Count; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis; D003012:Microbial Collagenase / Q000096:biosynthesis; D008934:Mitogens / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D008934:Mitogens; D010455:Peptides; D011458:Prostaglandins E; D014212:Tretinoin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003907:Dexamethasone; D003012:Microbial Collagenase; D013936:Thymidine; D007213:Indomethacin