Functional localization of proprotein-convertase furin and its substrate TGFbeta in EGF receptor-expressing gastric chief cells.

Furin, a proprotein-convertase, is distributed in the upper third layer and the lower quarter region of the rat gastric gland. We previously identified the upper furin-positive cells as parietal cells, and here, we identify the lower furin-positive cells as chief cells. Chief cells express three isoforms of transforming growth factor beta (TGFbeta), whose precursor requires cleavage by furin for its activation. When the chief cell mass was decreased in rats by adrenalectomy, pepsinogen-, furin-, and TGFbeta-positive cells were also reduced. Stimulation of mouse chief cell primary-cultures with transforming growth factor alpha (TGFalpha) induced an increase in the expression of furin and TGFbeta mRNAs and in the formation of mature TGFbeta. Since parietal cells are known to express a high level of the epidermal growth factor (EGF) -family growth factors and chief cells strongly express EGF receptors (EGF-R), we suggest that chief cells receive the EGF-R signal from parietal cells in a paracrine fashion and regulate parietal cell mass by controlling the formation of mature TGFbeta.