PHENOTYPIC AND FUNCTIONAL FEATURES OF MYOFIBROBLASTS IN SHEEP FETAL WOUNDS
PHENOTYPIC AND FUNCTIONAL FEATURES OF MYOFIBROBLASTS IN SHEEP FETAL WOUNDS
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DOI：
10.1046/j.1432-0436.1994.5630173.x
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发表时间：
1994-05-01
期刊：
影响因子：
2.9
通讯作者：
GABBIANI, G
中科院分区：
文献类型：
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作者：
ESTES, JM;VANDEBERG, JS;GABBIANI, G
肌成纤维细胞是一种间充质细胞，其功能和结构特征与成纤维细胞和平滑肌细胞相同。这些细胞在伤口闭合和愈合的病理后遗症中发挥着关键作用。成年人和实验动物的研究表明，肌成纤维细胞在伤口收缩期间暂时表达α-平滑肌肌动蛋白（ASMA），在纤维收缩疾病期间更持久地表达α-平滑肌肌动蛋白（ASMA）。然而，尚不清楚这种细胞是否对子宫内的组织修复有任何贡献。胎儿动物模型的实验工作表明，胎儿皮肤的伤口修复是通过表皮附属物的重建和真皮胶原网络的有组织恢复来实现的。胎羔伤口愈合研究表明，从无疤痕组织修复到疤痕形成愈合的转变发生在妊娠晚期。在这项研究中，我们使用透射电子显微镜 (TEM) 和 ASMA 免疫组织化学检查了胎羊羔伤口中肌成纤维细胞的个体发育，使用透射电子显微镜 (TEM) 和 ASMA 免疫组织化学。与妊娠晚期胎儿伤口肉芽组织相比，观察到早期和晚期胎儿伤口肉芽组织中 ASMA 含量存在显着差异：在妊娠 75 天时形成的伤口中不存在 ASMA，但在妊娠 75 天时伤口中存在 ASMA。妊娠 100 天和 120 天（足月 = 145 天）时伤口中的含量逐渐增加。 TEM 研究还证明了微丝束的逐步发展和组织。在发育早期，微丝束稀疏且杂乱，但随着妊娠的进展，微丝束变得更加普遍并形成紧密平行的排列。微丝束的组织也伴随着纤维连接的形成。因此，肉芽组织肌成纤维细胞中的 ASMA 表达似乎与疤痕形成的愈合有关。额外的体外实验表明，从 75、100 和 120 天妊娠羔羊的肉芽组织培养的大多数成纤维细胞表达 ASMA，这表明胎牛血清中存在的因子即使在体内不表达该蛋白的成纤维细胞中也可以诱导 ASMA 表达。我们的观察表明，胎儿肌成纤维细胞响应于损伤而发生个体发生变化。体内并表明局部因素可能调节妊娠期间肌成纤维细胞的可变表型。这些结果对病理性疤痕的治疗具有重要意义。
The myofibroblast is a mesenchymal cell with functional and structural characteristics in common with fibroblasts and smooth muscle cells. These cells play a critical role in wound closure and in the pathologic sequelae of healing. It has been shown in adult humans and experimental animals that the myofibroblast expresses alpha -smooth muscle actin (ASMA) temporarily during wound contraction and more persistently during fibrocontractive diseases; however, it is unclear whether this cell makes any contribution to tissue repair in utero. Experimental work in fetal animal models has demonstrated that wound repair in fetal skin occurs by reconstitution of epidermal appendages and organized restoration of the dermal collagen network. Fetal lamb wound healing studies have shown that a transition from scarless tissue repair to healing with scar formation occurs late in gestation.In this study we examined the ontogeny of myofibroblasts- in fetal lamb wounds at early through late gestation, using transmission electron microscopy (TEM) and ASMA immunohistochemistry.Dramatic differences were observed in ASMA content of early as compared to late gestation fetal wound granulation tissue: ASMA was absent in wounds made at 75 days gestation but was present in progressively greater amounts in wounds made at 100 and 120 days gestation (term=145 days). TEM studies also demonstrated progressive development and organization of microfilament bundles. Early in development microfilament bundles were sparse and disorganized, but as gestation progressed the bundles became more prevalent and formed tightly parallel arrangements. The organization of microfilament bundles was also accompanied by fibronexus formation. Thus, the ASMA expression in granulation tissue myofibroblasts appears in relation to healing with scar formation.Additional in vitro experiments demonstrated that the majority of fibroblasts cultured from granulation tissue of 75, 100 and 120 days gestation lambs expressed ASMA, suggesting that factors present in fetal calf serum can induce ASMA expression even in fibroblasts not expressing this protein in vivo.Our observations demonstrate an ontogenic change in the fetal myofibroblast in response to injury in vivo and suggest that local factors may regulate the variable phenotype of myofibroblasts during gestation. These results have implications for the therapy of pathologic scarring.