Raghunath M, Tschödrich-Rotter M, Sasaki T, Meuli M, Chu M L, Timpl R
Department of Dermatology, University of Münster, Germany.
J Invest Dermatol. 1999 Jan;112(1):97-101. doi: 10.1046/j.1523-1747.1999.00483.x.
The fibulins represent a novel family of extracellular matrix proteins. We report the temporo-spatial expression of fibulin-2 in skin regenerating from keratinocyte autografts. In normal dermis, fibulin-2 was associated with the fibrillin-containing microfibrillar apparatus, except for the portion immediately adjacent to the dermo-epidermal junction. In contrast, early regenerating dermis showed numerous fusiform fibrillin-microfibrils along the basement membrane, whereas fibulin-2 was present in a distinct and separate layer below. Both proteins formed independent fibrillar systems also in the reticular dermis without significant colocalization; however, over time both fibril systems became congruent: after 4 mo there was extensive colocalization of fibulin-2/fibrillin in the reticular dermis, after 17 and 24 mo this also occurred in the papillary dermis. Simultaneous visualization of fibulin-2 and fibronectin revealed an inverse pattern: complete colocalization at 7 d and discordant distribution 17-24 mo after grafting. In particular, the fibrillar fibronectin pattern at early time points changed into a faint granular distribution throughout the dermis and along the subbasement membrane region as in normal skin. Dermal fibroblast cultures showed that fibrillin and fibronectin participated in distinct fibrillar systems; however, fibulin-2 colocalized with either protein. We propose that, in regenerating skin, fibulin-2 is a late component of the cutaneous microfibrillar apparatus with an earlier existence in a fibrillar matrix mediated by fibronectin. This suggests interaction of fibulin-2 with both fibronectin fibrils and fibrillin microfibrils, and is consistent with in vitro binding data.
纤维连接蛋白代表了一类新的细胞外基质蛋白家族。我们报告了纤维连接蛋白-2在角质形成细胞自体移植皮肤再生过程中的时空表达情况。在正常真皮中，除了紧邻真皮-表皮交界处的部分外，纤维连接蛋白-2与含原纤蛋白的微纤维装置相关。相比之下，早期再生真皮在基底膜沿线显示出大量梭形原纤蛋白微纤维，而纤维连接蛋白-2则存在于下方一个独特且分离的层中。这两种蛋白在网状真皮中也形成独立的纤维系统，且无明显共定位；然而，随着时间推移，两个纤维系统变得一致：4个月后，纤维连接蛋白-2/原纤蛋白在网状真皮中有广泛的共定位，17个月和24个月后，在乳头层真皮中也出现这种情况。纤维连接蛋白-2和纤连蛋白的同时可视化显示出相反的模式：移植后7天完全共定位，17 - 24个月分布不一致。特别是，早期时间点的纤维状纤连蛋白模式在整个真皮以及基底膜下区域变为微弱的颗粒状分布，如同正常皮肤那样。真皮成纤维细胞培养显示，原纤蛋白和纤连蛋白参与不同的纤维系统；然而，纤维连接蛋白-2与这两种蛋白中的任何一种都共定位。我们提出，在再生皮肤中，纤维连接蛋白-2是皮肤微纤维装置的晚期成分，在由纤连蛋白介导的纤维状基质中更早存在。这表明纤维连接蛋白-2与纤连蛋白纤维和原纤蛋白微纤维都有相互作用，并且与体外结合数据一致。
