AUTOCRINE REGULATION OF GROWTH IN CULTURED HUMAN INTESTINAL MUSCLE BYGROWTH-FACTORS

Background & Aims: Transforming growth factor (TGF)-alpha, insulin-lik e growth factor (IGF)-I, and TGF-beta 1 are expressed in vivo by intes tinal smooth muscle. The aim of this study was to determine whether th ese growth factors were produced by human intestinal muscle cells in c ulture and to identify their roles in regulating growth. Methods: Musc le cells were examined at various times in culture: during vapid growt h (day 3), at confluence (day 7), and after confluence (day 14). Growt h factor production was measured by radioimmunoassay or enzyme-linked immunosorbent assay. Growth was measured from [H-3]thymidine incorpora tion. Results: Production of pro-TGF-alpha and TGF-alpha (1550 +/- 100 and 1260 +/- 150 pg/mg protein, respectively) and free IGF-I (86.2 +/ - 23.7 ng/mg protein) was highest during rapid growth and 3-40-fold lo wer later in culture. Production of soluble and latent TGF-beta 1 was highest in postconfluent cells (280 +/- 74 and 4320 +/- 610 pg/mg prot ein, respectively) and 4-7 fold lower earlier in culture. TGF-alpha an d IGF-I caused concentration-dependent stimulation of growth in rapidl y growing cells. TGF-beta 1 caused concentration-dependent inhibition of growth predominantly in postconfluent cells. Neutralizing antibodie s to TGF-alpha or IGF-I inhibited growth and neutralizing antibody to TGF-beta augmented growth. Conclusions: Human intestinal muscle cells produce TGF-alpha, IGF-I, and TGF-beta 1 in a time-dependent reciproca l fashion that parallels their effects on growth.