TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin.
TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin.
复制标题
DOI：
10.1016/j.taap.2014.02.010
复制
发表时间：
2014-05-01
影响因子：
3.8
通讯作者：
Allen-Hoffmann, B. Lynn
中科院分区：
文献类型：
--
作者：
De Abrew, K. Nadira;Thomas-Virnig, Christina L.;Rasmussen, Cathy A.;Bolterstein, Elyse A.;Schlosser, Sandy J.;Allen-Hoffmann, B. Lynn
皮肤的表皮是抵御环境的第一道防线。利用人体皮肤三维模型研究了环境污染物2，3，7，8-四氯二苯并-对二恶英(TCDD)诱导的组织特异性表型。用TCDD连续处理器官培养的人角质形成细胞，除了先前报道的过度角化外，还导致基底层和直接基底层的角质形成细胞之间的细胞间隙以及基底膜变薄。这些组织重塑事件在时间上先于细胞外基质降解酶-基质金属蛋白酶-10(MMP10)的表达变化。在器官培养中，经TCDD处理后，基质金属蛋白酶-10的mRNA和蛋白被高度诱导。经TCDD处理的单层培养的Q-PCR和免疫印迹结果，以及TCDD处理的器官培养的间接免疫荧光和免疫印迹分析表明，MMP10特异性地由表皮角质形成细胞表达，而不是真皮成纤维细胞。角质形成细胞来源的基质金属蛋白酶-10蛋白随着时间的推移在器官培养的真皮中积累。TCDD诱导的器官培养中的表皮表型被角质形成细胞特异性表达的金属蛋白酶组织抑制物-1，一种已知的基质金属蛋白酶-10的抑制物所减弱。这些研究表明，MMP10和其他MMPs可能与TCDD处理的器官培养基底膜、基底层角质形成细胞层和角化层的表型有关。我们的研究揭示了一种新的机制，通过这种机制，上皮-间质微环境以组织特异性的方式改变，从而在人类皮肤的毛囊间表皮中诱导结构和功能病理。
The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial-stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin.
登录
查看更多内容
影响因子：
11.2
作者：
Symowicz, Jaime;Adley, Brian P.;Stack, M. Sharon
通讯作者：
Stack, M. Sharon
DOI：
10.1046/j.1432-1327.1998.2530067.x
发表时间：
1998-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Nakamura, H;Fujii, Y;Okada, Y
通讯作者：
Okada, Y
影响因子：
10.4
作者：
BROWN, NM;LAMARTINIERE, CA
通讯作者：
LAMARTINIERE, CA
影响因子：
3.3
作者：
Krampert, M;Bloch, W;Werner, S
通讯作者：
Werner, S
影响因子：
3.8
作者：
Loertscher, JA;Sattler, CA;Allen-Hoffmann, BL
通讯作者：
Allen-Hoffmann, BL