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

机械应力对瘢痕疙瘩成纤维细胞凋亡的影响分析

• 批准号: 13671876
• 负责人: YOSHIMOTO Shinya
• 金额: $ 2.24万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671876/
• 关键词: keloid; fibroblasts; apoptosis; p53; Bax; MAP Kinase; p38; Mechanical stress; cDNA array; 2軸回転式細胞培養装置; 肥厚性瘢痕; 細胞表面分子

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.

瘢痕疙瘩的特征是成纤维细胞的增殖和细胞外基质的增多。成纤维细胞过度生长和较低的凋亡率与瘢痕疙瘩的发病机制有关。细胞凋亡信号通路功能障碍被认为是瘢痕疙瘩发生发展的机制之一。为了研究导致功能障碍的细胞信号因素，抗代谢药物被用作瘢痕疙瘩来源细胞异常反应的诱导剂。比较了瘢痕疙瘩成纤维细胞(KF)和正常皮肤成纤维细胞(NF)对N-甲基-N‘-硝基-N-亚硝基(MNNG)抗增殖作用的敏感性。在KF和NF细胞中，观察到治疗后P53和Bax的表达水平增加。此外，人成纤维细胞在机械应力自由落体暴露后极易发生凋亡。机械应激后4h，成纤维细胞胞核P53和胞浆Bax表达增强。因此，这些分子可能参与了MNNG对KF和NF的细胞毒作用。

项目成果

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Tatsuya Sugita: "Hypermutable change of human UV'-1 cells by p53 overexpression"Biochemical Biophysical Research Communications. 289. 756-762 (2001)

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