The α and β subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation

The α and β subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation
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DOI:
10.1038/sj.jid.5700675
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发表时间:
2007-05-01
影响因子:
6.5
通讯作者:
Stoecker, Walter
Stoecker, Walter
中科院分区:
医学1区
文献类型:
--
作者:
Becker-Pauly, Christoph;Hoewel, Markus;Stoecker, Walter

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锌内肽酶meprin (EC 3.4.24.18)在肠、肾小管刷状缘膜、肠白细胞和某些癌细胞中表达,提示其在上皮分化和细胞迁移中起作用。通过RT-PCR和免疫印迹技术,我们发现meprin在人体皮肤中也有表达。免疫组织化学显示,这两个meprin亚基位于人表皮的不同细胞层中。Meprin α表达于基底层,而Meprin β则存在于角质层下方的颗粒层细胞中。在过度增生的表皮中,如寻常型牛皮癣,meprin α的表达从表皮的底层明显转移到最上层。表达模式表明这两个亚基在皮肤中的功能不同。重组meprin α和β对成人低钙高温角质形成细胞的不同影响支持了这一假设。在这里,β诱导细胞形态发生剧烈变化,细胞数量减少,表明在终末分化中起作用,而meprin a不影响细胞活力,可能在基底角化细胞增殖中起作用。
The zinc endopeptidase meprin (EC 3.4.24.18) is expressed in brush border membranes of intestine and kidney tubules, intestinal leukocytes, and certain cancer cells, suggesting a role in epithelial differentiation and cell migration. Here we show by RT-PCR and immunoblotting that meprin is also expressed in human skin. As visualized by immunohistochemistry, the two meprin subunits are localized in separate cell layers of the human epidermis. Meprin alpha is expressed in the stratum basale, whereas meprin beta is found in cells of the stratum granulosum just beneath the stratum corneum. In hyperproliferative epidermis such as in psoriasis vulgaris, meprin alpha showed a marked shift of expression from the basal to the uppermost layers of the epidermis. The expression patterns suggest distinct functions for the two subunits in skin. This assumption is supported by diverse effects of recombinant meprin alpha and beta on human adult low-calcium high-temperature keratinocytes. Here, beta induced a dramatic change in cell morphology and reduced the cell number, indicating a function in terminal differentiation, whereas meprin a did not affect cell viability, and may play a role in basal keratinocyte proliferation.