ANALYSIS OF EFFECTS OF MECHANICAL STRESS ON APOPTOSIS OF KELOID DERIVED FIBROBLASTS

瘢痕疙瘩的特征是成纤维细胞的增殖和细胞外基质的增加。成纤维细胞的过度生长和较低的凋亡率与瘢痕疙瘩的病因有关。凋亡信号通路的功能障碍被认为是瘢痕疙瘩形成的机制之一。为了研究导致功能障碍的细胞信号因子，研究人员利用抗代谢药物作为瘢痕疙瘩来源细胞异常反应的诱导剂。比较了瘢痕疙瘩皮肤成纤维细胞（KF）和正常皮肤成纤维细胞（NF）对n -甲基-n '-硝基-n -亚硝基胍（MNNG）抗增殖作用的敏感性。在KF和NF细胞中，治疗后观察到p53和Bax水平升高。此外，人成纤维细胞在自由落体机械应力暴露后极易发生凋亡。机械应力暴露后4 h成纤维细胞中核p53和细胞质Bax的表达增加。因此，这些分子可能有助于MNNG在KF和NF中的细胞毒性作用。

Keloids are characterized by the proliferation of fibroblasts and increased accumulation of extracellular matrix. Excessive growth of fibroblasts and lower rate of apoptosis has been implicated in the etiology of keloids. Malfunction of apoptotic signaling pathways are thought to be one of mechanisms underlying tumorigenic growth of keloid scar. To investigate cellular signaling factors responsible for the malfunction, antimetabolic agents were utilized as an inducer of unusual response in keloid-derived cells. Fibroblasts from keloid skin (KF) and those from normal skin (NF) were compared with respect to their sensitivity to the anti-proliferative effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In KF and NF cells, enhanced levels of p53 and Bax amounts were observed after the treatment. Moreover, human fibroblasts were highly susceptible to apoptosis after mechanical stress exposure by a free-fall. The expression of nuclear p53 and cytoplasmic Bax in the fibroblasts increased at 4 h after mechanical stress exposure. Thus, these molecules may contribute cytotoxic effects of MNNG in KF and NF.