Age-related changes in the proteoglycans of human skin -: Specific cleavage of decorin to yield a major catabolic fragment in adult skin
Age-related changes in the proteoglycans of human skin -: Specific cleavage of decorin to yield a major catabolic fragment in adult skin
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DOI：
10.1074/jbc.m300124200
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发表时间：
2003-05-09
影响因子：
4.8
通讯作者：
Caplan, AI
中科院分区：
文献类型：
--
作者：
Carrino, DA;Önnerfjord, P;Caplan, AI
随着年龄的增长，皮肤会发生巨大的变化，包括形态、生理和机械性能的变化。细胞外基质分子也会发生变化，这些变化可能会导致皮肤物理特性随年龄的整体变化。在人类皮肤提取液中检测到的主要蛋白多糖是核心蛋白聚糖和魔芋多糖。此外，成人皮肤含有截短形式的装饰素，而胎儿皮肤含有几乎检测不到的这种截短的装饰素水平。对这个分子的分析表明，它是核心蛋白聚糖的分解代谢片段，而不是剪接变异体。利用针对核心蛋白的抗体探针，发现Decorant缺少核心蛋白核心蛋白的羧基末端部分。基质辅助激光解吸/电离飞行时间质谱仪的进一步分析表明，脱脂蛋白的羧基末端位于核心蛋白的Phe(170)。这一结果表明，核心蛋白的氨基末端占成熟核心蛋白分子的43%。这种结构与核心蛋白的选择性剪接不一致，表明核心蛋白是核心蛋白的分解代谢片段。针对Decorant的羧基末端产生了一种新的表位抗血清--抗VRKVTF。这种抗血清不识别免疫印迹测试的任何皮肤蛋白多糖样品中的完整核心蛋白，但识别每一个测试的核心蛋白。抗VRKVTF的结果证实了脱脂蛋白的羧基末端的鉴定。表面等离子体共振分析表明，饰面对I型胶原的亲和力比饰面小100倍。这一观察结果与Decorunt的结构分析相关联，因为它缺少先前被证明对与I型胶原相互作用很重要的核心蛋白。对核心蛋白聚糖分解代谢片段的检测表明，这种蛋白多糖存在一条特定的分解代谢途径。由于核心蛋白聚糖具有影响胶原纤维形成的能力，其分解代谢可能对真皮胶原蛋白网络具有重要的功能意义。
Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe(170) of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the capacity of decorin to influence collagen fibrillogenesis, catabolism of decorin may have important functional implications with respect to the dermal collagen network.