Proprotein-processing endoprotease furin controls the growth and differentiation of gastric surface mucous cells

Gastric surface mucous cells originate from progenitor cells at the isthmus of the gastric gland, from where the cells migrate to the luminal surface. With migration they form secretory granules and express TGF alpha. We found that proprotein-processing endoprotease furin-positive cells were layered around the upper one fourth of the gastric glands of adult rats, whereas they were distributed along an outer epithelial layer in fetal rats. Because the furin-positive cell layer was localized from the upper cell proliferating zone to the less proliferating pit-cell region in the gastric gland unit, we examined the role of furin in the growth and differentiation of surface mucous cells by using the cell line, GSM06. This cell line is derived from the gastric surface mucous cells of transgenic mice harboring the temperature-sensitive simian virus 40 T antigen. At T antigen-active temperature (33 degrees C), the cells grew to confluency, whereas at T antigen-inactive temperature (39 degrees C), the cells ceased growing. At 33 degrees C, the cells exhibited a high level of furin expression with a negligible level of periodic acid Schiff (PAS)-positive materials and a low level of TGF alpha. In contrast, at 39 degrees C the cells produced a high level of PAS-positive materials, TGF alpha, and secretory granules, with a negligible level of furin expression. To further examine the role of furin, we established a GSM06 cell line introduced with either a sense or an antisense furin cDNA. The cells with sense furin expression produced fewer PAS-positive materials and a low level of TGF alpha even at 39 degrees C, whereas the cells with antisense furin expression exhibited more PAS-positive materials and TGF alpha even at 33 degrees C. When furin expression was suppressed by its antisense oligonucleotide, the cell growth was retarded with enhanced expression of the differentiated characteristics. Thus, we conclude that furin is instrumental in controlling the growth of the surface mucous cells.