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

Functional localization of proprotein-convertase furin and its substrate TGFβ in EGF receptor-expressing gastric chief cells
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DOI:
10.1080/0897719042000201659
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发表时间:
2004-03-01
期刊:
影响因子:
1.8
通讯作者:
Takeuchi, T
Takeuchi, T
中科院分区:
生物学4区
文献类型:
--
作者:
Fujisawa, T;Kamimura, H;Takeuchi, T

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弗林蛋白酶是一种前蛋白转化酶,分布于大鼠胃腺的上三层和下四分之一区域。我们以前确定上部弗林蛋白酶阳性细胞为壁细胞,在这里,我们确定下部弗林蛋白酶阳性细胞为主细胞。主细胞表达转化生长因子β(TGF β)的三种同种型,其前体需要弗林蛋白酶切割以使其活化。当大鼠肾上腺切除术后主细胞群减少时,胃蛋白酶原、弗林蛋白酶和TGF β阳性细胞也减少。用转化生长因子α(TGFalpha)刺激小鼠主细胞原代培养物可诱导弗林蛋白酶和TGFbeta mRNA的表达增加以及成熟TGFbeta的形成。由于壁细胞是已知的表达高水平的表皮生长因子(EGF)家族的生长因子和主细胞强烈表达EGF受体(EGF-R),我们建议,主细胞接收EGF-R信号从壁细胞的旁分泌方式和调节壁细胞质量通过控制成熟TGF β的形成。
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.