Enhanced expression of transforming growth factor (TGF) -alpha precursor and TGF-beta1 during Paneth cell regeneration.

An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing and rapid regeneration of Paneth cells, which have a large amount of zinc in their cytoplasmic granules. We examined the expression pattern of transforming growth factor (TGF) -alpha and TGF-beta1 in this regenerative process. Messenger RNA expression of TGF-alpha and TGF-beta1 reached their peaks at 12 and 24 hr after dithizone injection, respectively. Protein expression of TGF-alpha precursor and TGF-beta1 increased to a maximum at 24 and 72 hr, respectively. Their immunoreactivities were localized in the epithelial cells in the vicinity of Paneth cells, whereas they were prominent in the upper half of the crypts in control rats. In conclusion, destruction of Paneth cells induced TGF-alpha precursor expression, followed by an increase of TGF-beta1 especially in the crypt bases. This unique expression pattern of two growth factors may be involved in rapid regeneration of Paneth cells.