The Versican G1 Fragment and Serum-Derived Hyaluronan-Associated Proteins Interact and Form a Complex in Granulation Tissue of Pressure Ulcers
The Versican G1 Fragment and Serum-Derived Hyaluronan-Associated Proteins Interact and Form a Complex in Granulation Tissue of Pressure Ulcers
复制标题
Versican G1 片段和血清来源的透明质酸相关蛋白在压疮肉芽组织中相互作用并形成复合物
DOI：
10.1016/j.ajpath.2017.10.015
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Isogai Zenzo
中科院分区：
文献类型：
--
作者：
Murasawa Yusuke;Nakamura Hiroyuki;Watanabe Ken;Kanoh Hiroyuki;Koyama Emiko;Fujii Satoshi;Kimata Koji;Zako Masahiro;Yoneda Masahiko;Isogai Zenzo
富含透明质酸（HA）的细胞外基质在组织重塑过程中起着动态作用。HA相关蛋白（HA associated protein，SHAP）是与HA结合的重要分子，与α-胰蛋白酶间抑制剂（inter-α-trypsin inhibitor，INT）的重链相对应。Versican G1结构域片段（VG 1F）是由蛋白水解产生的，存在于重塑组织或成熟真皮中。然而，VG 1F的大复合物形成尚未阐明。因此，我们研究了含有VG 1F的大复合物在以慢性难治性伤口为特征的压疮中的作用。VG 1F与SHAP-HA共定位于肉芽组织的特定区域，但不与β-胡萝卜素-1共定位。一个独特的VG 1F-SHAP-HA复合物分离肉芽组织使用凝胶过滤色谱法和随后的氯化铯梯度超离心分离条件下。与此分子组成一致，重组多功能蛋白聚糖G1，而不是多功能蛋白聚糖G3，与两个重链的间-α-胰蛋白酶抑制剂相互作用。在成纤维细胞培养物中添加重组VG 1增强了VG 1F-SHAP-HA复合物在细胞周围细胞外基质中的沉积。与其他含有VG 1F的大复合物，包括真皮VG 1F聚集体，多功能蛋白聚糖结合的微纤维，和完整的多功能蛋白聚糖的比较，突出了组织特异性组织的HA丰富的细胞外基质形成含有多功能蛋白聚糖和SHAP。VG 1F-SHAP-HA复合物在人压力溃疡的水肿肉芽组织中以及在潮湿伤口愈合的小鼠模型中的发炎阶段中被特异性地检测到，这表明该复合物提供了适合于炎症反应的富含HA的基质。
The hyaluronan (HA)–rich extracellular matrix plays dynamic roles during tissue remodeling. Versican and serum-derived HA-associated protein (SHAP), corresponding to the heavy chains of inter-α-trypsin inhibitor, are major HA-binding molecules in remodeling processes, such as wound healing. Versican G1-domain fragment (VG1F) is generated by proteolysis and is present in either remodeling tissues or the mature dermis. However, the macrocomplex formation of VG1F has not been clarified. Therefore, we examined the VG1F-containing macrocomplex in pressure ulcers characterized by chronic refractory wounds. VG1F colocalized with SHAP-HA in specific regions of the granulation tissue but not with fibrillin-1. A unique VG1F-SHAP-HA complex was isolated from granulation tissues using gel filtration chromatography and subsequent cesium chloride–gradient ultracentrifugation under dissociating conditions. Consistent with this molecular composition, recombinant versican G1, but not versican G3, interacted with the two heavy chains of inter-α-trypsin inhibitor. The addition of recombinant VG1 in fibroblast cultures enhanced VG1F-SHAP-HA complex deposition in the pericellular extracellular matrix. Comparison with other VG1F-containing macrocomplexes, including dermal VG1F aggregates, versican-bound microfibrils, and intact versican, highlighted the tissue-specific organization of HA-rich extracellular matrix formation containing versican and SHAP. The VG1F-SHAP-HA complex was specifically detected in the edematous granulation tissues of human pressure ulcers and in inflamed stages in a mouse model of moist would healing, suggesting that the complex provides an HA-rich matrix suitable for inflammatory reactions.