Hembry R M, Bernanke D H, Hayashi K, Trelstad R L, Ehrlich H P
Am J Pathol. 1986 Oct;125(1):81-9.
The healing process of an open wound as effected by wound contraction is complete by 3 weeks in the normal mouse. In contrast, its onset is delayed by 3 weeks and complete healing requires 6 weeks in the tight skin mouse (TSM), a mutant mouse strain with the autosomal dominant gene for tight skin. Possible mechanisms for this delay were evaluated. The frequency and distribution of myofibroblasts were studied during the 3-week delay in wound contraction by actin staining and electron microscopy. It was determined, by electron microscopy and phalloidin staining, that myofibroblasts were found in high density in noncontracting TSM wounds. Electron microscopy showed, however, that these myofibroblasts were surrounded by a pericellular matrix that separated their surface from adjacent collagen fibers. No pericellular matrix was found around cells in granulation tissue of normal mice. At 3 weeks, as TSM wounds began to contract, the number and intensity of cells stained by phalloidin in this tissue was less than that seen earlier. The pericellular matrix was fragmented at this time, and cell surface and collagen fiber associations were apparent. Finally, at 5 weeks, when wound contraction was well developed in the TSM, only a small area in the center of the healing wound beneath the epidermis contained phalloidin-positive myofibroblasts. Electron-microscopic examination of the residual granulation tissue at this time revealed the complete absence of the pericellular matrix. It is postulated that during the 3-week delay in wound closure, the presence of a localized pericellular matrix prevents the interaction between cells and collagen fibers necessary for the reorganization of collagen. It is also thought that the tightly adherent uninjured skin surrounding the healing wound may cause delayed wound closure. There was no evidence that the absence of myofibroblasts is responsible for delayed wound contraction.
在正常小鼠中，开放性伤口通过伤口收缩实现的愈合过程在3周内完成。相比之下，在紧皮小鼠（TSM）中，这一过程的开始延迟了3周，完全愈合需要6周。TSM是一种具有常染色体显性紧皮基因的突变小鼠品系。对这种延迟的可能机制进行了评估。通过肌动蛋白染色和电子显微镜研究了伤口收缩延迟3周期间肌成纤维细胞的频率和分布。通过电子显微镜和鬼笔环肽染色确定，在未收缩的TSM伤口中发现肌成纤维细胞密度很高。然而，电子显微镜显示，这些肌成纤维细胞被细胞周围基质包围，该基质将其表面与相邻的胶原纤维分隔开。在正常小鼠肉芽组织的细胞周围未发现细胞周围基质。3周时，随着TSM伤口开始收缩，该组织中被鬼笔环肽染色的细胞数量和强度低于早期观察到的情况。此时细胞周围基质破碎，细胞表面与胶原纤维的关联明显。最后，在5周时，当TSM伤口收缩良好时，仅在表皮下方愈合伤口中心的一小区域含有鬼笔环肽阳性的肌成纤维细胞。此时对残留肉芽组织的电子显微镜检查显示细胞周围基质完全缺失。据推测，在伤口闭合延迟的3周期间，局部细胞周围基质的存在阻止了细胞与胶原纤维之间进行胶原重组所必需的相互作用。还认为，愈合伤口周围紧密附着的未受伤皮肤可能导致伤口闭合延迟。没有证据表明肌成纤维细胞的缺失是伤口收缩延迟的原因。
