Butzelaar Liselotte, Niessen Frank B, Talhout Wendy, Schooneman Dennis P M, Ulrich Magda M, Beelen Robert H J, Mink van der Molen Aebele B
Department of Plastic, Reconstructive and Hand Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Wound Repair Regen. 2017 Sep;25(5):758-766. doi: 10.1111/wrr.12574. Epub 2017 Nov 2.
The purpose of this study was to examine extracellular matrix composition, vascularization, and immune cell population of skin sites prone to keloid formation. Keloids remain a complex problem, posing esthetical as well as functional difficulties for those affected. These scars tend to develop at anatomic sites of preference. Mechanical properties of skin vary with anatomic location and depend largely on extracellular matrix composition. These differences in extracellular matrix composition, but also vascularization and resident immune cell populations might play a role in the mechanism of keloid formation. To examine this hypothesis, skin samples of several anatomic locations were taken from 24 human donors within zero to 36 hours after they had deceased. Collagen content and cross-links were determined through high-performance liquid chromatography. The expression of several genes, involved in extracellular matrix production and degradation, was measured by means of real-time PCR. (Immuno)histochemistry was performed to detect fibroblasts, collagen, elastin, blood vessels, Langerhans cells, and macrophages. Properties of skin of keloid predilections sites were compared to properties of skin from other locations (nonpredilection sites [NPS]). The results indicated that there are site specific variations in extracellular matrix properties (collagen and cross-links) as well as macrophage numbers. Moreover, predilection sites (PS) for keloid formation contain larger amounts of collagen compared to NPS, but decreased numbers of macrophages, in particular classically activated CD40 positive macrophages. In conclusion, the altered (histological, protein, and genetic) properties of skin of keloid PS may cause a predisposition for and contribute to keloid formation.
本研究的目的是检查易于形成瘢痕疙瘩的皮肤部位的细胞外基质组成、血管形成和免疫细胞群体。瘢痕疙瘩仍然是一个复杂的问题，给患者带来美学和功能上的困难。这些瘢痕往往在偏好的解剖部位形成。皮肤的机械性能因解剖位置而异，并且在很大程度上取决于细胞外基质的组成。细胞外基质组成、血管形成和常驻免疫细胞群体的这些差异可能在瘢痕疙瘩形成机制中起作用。为了验证这一假设，在24名人类供体死亡后的0至36小时内，从其多个解剖部位采集了皮肤样本。通过高效液相色谱法测定胶原蛋白含量和交联情况。通过实时聚合酶链反应测量参与细胞外基质产生和降解的几个基因的表达。进行（免疫）组织化学以检测成纤维细胞、胶原蛋白、弹性蛋白、血管、朗格汉斯细胞和巨噬细胞。将瘢痕疙瘩好发部位的皮肤特性与其他部位（非好发部位[NPS]）的皮肤特性进行比较。结果表明，细胞外基质特性（胶原蛋白和交联）以及巨噬细胞数量存在部位特异性差异。此外，与非好发部位相比，瘢痕疙瘩形成的好发部位（PS）含有更多的胶原蛋白，但巨噬细胞数量减少，尤其是经典激活的CD40阳性巨噬细胞。总之，瘢痕疙瘩好发部位皮肤的（组织学、蛋白质和基因）特性改变可能导致瘢痕疙瘩形成的易感性并促成瘢痕疙瘩的形成。
