ROLE OF TRANSFORMING GROWTH-FACTOR-BETA IN THE RESTITUTION OF INJUREDGUINEA-PIG GASTRIC-MUCOSA IN-VITRO

The role of transforming growth factor-beta (TGF-beta) in restitution was examined in intact sheets of injured guinea pig gastric mucosa in which the epithelial cell-collagen interaction can be quantitatively e valuated. The luminal surface of intact sheets of in vitro guinea pig gastric mucosa was injured by exposure to 1.25 mol/l NaCl for 10 min. Restitution was evaluated by measurement of transmucosal electrical re sistance and [H-3]mannitol flux before and after injury. Recovery of e lectrical resistance and [H-3]mannitol flux was retarded by inhibition of endogenous TGF-beta with either aprotinin or anti-TGF-beta antibod y; effects were restored by human recombinant TGF-beta 1. During inhib ition of endogenous TGF-beta, type IV collagen accelerated the recover y. Inhibition of reconstruction of the basement membrane by simultaneo us addition of cis-4-OH-L-proline and anti-type IV collagen completely abolished the enhancement of the recovery by TGF-beta 1. These result s suggest that endogenous TGF-beta is required for restitution to occu r in guinea pig gastric mucosa and that type IV collagen plays an impo rtant role in TGF-beta-abetted restitution.