Transforming growth factor-beta inhibits proliferation and maturation of cultured guinea pig gastric pit cells.

We studied the effects of transforming growth factor-beta1 (TGF-beta1) on guinea pig gastric mucous cells, cultured in serum-free conditions. Electron microscopy showed that most cells were pre-pit cells, characterized by the presence of a few secretory granules scattered in the cytoplasm. Epidermal growth factor (EGF) stimulated cell growth, [3H]glucosamine uptake, and accumulation of mucus granules positive for galactose oxidase-Schiff reaction. This EGF-induced maturation into pit cells was confirmed morphologically by the appearance of uniformly dense ovoid or spherical mucus granules packed in the ectoplasm. Western blotting with an antiphosphotyrosine antibody showed that TGF-beta1 did not inhibit the EGF-initiated tyrosine phosphorylation of the EGF receptor. Northern blotting with cDNA probes for c-fos and c-myc demonstrated that TGF-beta1 did not affect the EGF-induced expression of the transcripts. However, TGF-beta1-treated cells did not replicate and remained in an immature stage, even in the presence of EGF, suggesting a potential role of TGF-beta1 in the regulation of proliferation and differentiation of a pit cell lineage in vivo.