Functional Localization of Proprotein-convertase Furin and its Substrate TGFβ in EGF Receptor-expressing Gastric Chief Cells

Abstract

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 β (TGFβ), whose precursor requires cleavage by furin for its activation. When the chief cell mass was decreased in rats by adrenalectomy, pepsinogen-, furin-, and TGFβ-positive cells were also reduced. Stimulation of mouse chief cell primary-cultures with transforming growth factor α (TGFα) induced an increase in the expression of furin and TGFβ mRNAs and in the formation of mature TGFβ. 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 TGFβ.

• Chief cells
• EGF receptor
• Furin
• TGFβ
• Adrenalectomy
• TGFα, transforming growth factor α
• TGFβ, transforming growth factor β
• HB-EGF, heparin binding-EGF-like growth factor
• EGF-R, EGF receptor
• PMA, phorbol-12-myristate 13-acetate
• FITC, fluorescein isothiocyanate
• Cy3, indodicarbocianide