Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling.
Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling.
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DOI：
10.1038/labinvest.2010.181
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发表时间：
2011-04
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瘢痕挛缩被认为是由伤口愈合的重塑阶段期间的细胞收缩性引起的。细胞收缩性由非肌肉肌球蛋白II（NMMII）和肌动蛋白介导，但NMMII亚型A和B（IIA和II B）在重塑阶段的时空表达谱以及NMMII在瘢痕成纤维细胞组织重塑中的作用尚不清楚。人瘢痕组织IIA和IIB的免疫染色显示，这两种亚型在整个修复的重塑阶段的瘢痕组织中高度表达，并且在重塑阶段后表达水平恢复正常。人瘢痕组织β-、γ-和α-平滑肌肌动蛋白的免疫染色显示，所有亚型在修复的整个重塑阶段都一致表达。β-和γ-平滑肌肌动蛋白在整个真皮中广泛表达，而α-平滑肌肌动蛋白仅在真皮中局部表达。在体外，从瘢痕组织中分离的成纤维细胞比从正常组织中分离的成纤维细胞表达更多的IIA，并且瘢痕成纤维细胞比正常成纤维细胞更大程度地收缩胶原晶格。Blebbistatin用于证明NMMII在胶原晶格收缩中的功能。在正常组织中，成纤维细胞通过细胞外基质来屏蔽外部拉伸应力。在真皮损伤后和重塑期间，成纤维细胞暴露于刚度增加的基质。检查基质硬度对IIA和IIB表达的影响。IIA的表达是更大的成纤维细胞培养的胶原晶格与刚度增加，并在玻璃载玻片上培养的成纤维细胞相比，聚丙烯酰胺凝胶刚度为1千帕。总之，NMMII和肌动蛋白亚型表达的变化与修复的重塑阶段协调，NMMII随着基质硬度的增加而增加。随着NMMII表达增加，成纤维细胞收缩性也增加。
Scar contracture is believed to be caused by the cell contractility during the remodeling phase of wound healing. Cell contractility is mediated by non-muscle myosin II (NMMII) and actin, but the temporal-spatial expression profile of NMMII isoforms A and B (IIA and IIB) during the remodeling phase and the role of NMMII in scar fibroblast tissue remodeling are unknown. Human scar tissue immunostained for IIA and IIB showed that both isoforms were highly expressed in scar tissue throughout the remodeling phase of repair and expression levels returned to normal after the remodeling phase. Human scar tissue immunostained for β-, γ- and α-smooth muscle actin showed that all isoforms were consistently expressed throughout the remodeling phase of repair. The β- and γ-smooth muscle actin were widely expressed throughout the dermis, but α-smooth muscle actin was only locally expressed within the dermis. In vitro, fibroblasts explanted from scar tissue were shown to express more IIA than fibroblasts explanted from normal tissue and scar fibroblasts contracted collagen lattices to a greater extent than normal fibroblasts. Blebbistatin was used to demonstrate the function of NMMII in collagen lattice contraction. In normal tissue, fibroblasts are stress-shielded from external tensile stress by the extracellular matrix. After dermal injury and during remodeling, fibroblasts are exposed to a matrix of increased stiffness. The effect of matrix stiffness on IIA and IIB expression was examined. IIA expression was greater in fibroblasts cultured in collagen lattices with increasing stiffness, and in fibroblasts cultured on glass slides compared with polyacrylamide gels with stiffness of 1 kPa. In conclusion, NMMII and actin isoform expression changes coordinately with the remodeling phase of repair, and NMMII is increased as matrix stiffness increases. As NMMII expression increases, so does the fibroblast contractility.