Expression of apoptosis‐associated genes by human dermal scar fibroblasts

Expression of apoptosis‐associated genes by human dermal scar fibroblasts
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DOI:
10.1046/j.1524-475x.1999.00511.x
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发表时间:
1999-11
影响因子:
2.9
通讯作者:
D. Messadi;Anh Le;S. Berg;A. Jewett;Z. Wen;P. Kelly;C. Bertolami
D. Messadi;Anh Le;S. Berg;A. Jewett;Z. Wen;P. Kelly;C. Bertolami
中科院分区:
医学3区
文献类型:
--
作者:
D. Messadi;Anh Le;S. Berg;A. Jewett;Z. Wen;P. Kelly;C. Bertolami

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本研究的目的是确定异常细胞凋亡是否在病理性伤口愈合中起作用,如增生性瘢痕和瘢痕疙瘩形成所示。最近发现细胞凋亡参与肉芽组织和永久性瘢痕的发展之间的过渡。仍有待回答的问题是什么刺激在伤口愈合过程中启动细胞凋亡。相关的调节因子和途径在很大程度上尚未确定。我们通过检测正常皮肤和瘢痕疙瘩成纤维细胞的凋亡特征和途径,研究了这些细胞的异质性。使用Annexin-V-FITC结合试验对凋亡细胞进行定量分析,结果显示正常皮肤成纤维细胞培养物的凋亡细胞百分比是瘢痕疙瘩成纤维细胞培养物的两倍。为了研究凋亡途径和相关死亡相关基因,对暴露于抗Fas抗体和肿瘤坏死因子-α的成纤维细胞进行核糖核酸酶保护试验,以激活Fas/TNF受体凋亡途径。与正常皮肤成纤维细胞相比,瘢痕疙瘩成纤维细胞表现出凋亡相关基因的表达减少。
The purpose of this study was to determine if aberrant apoptosis plays a role in pathologic wound healing as manifested by hypertrophic scarring and keloid formation. Apoptosis has recently been found to participate in the transition between granulation tissue and the development of definitive scar. The question that remains to be answered is what stimuli initiate apoptosis during wound healing. Hitherto, regulatory factors and pathways involved have been largely undefined. We investigated heterogeneity among fibroblasts derived from normal skin and keloid scar, by examining apoptotic profiles and pathways for these cells. Quantitative analysis of apoptotic cells using an Annexin‐V‐FITC binding assay showed that normal skin fibroblast cultures were found to have a two‐fold higher percentage of apoptotic cells than did keloid fibroblast cultures. To study apoptotic pathways and related death‐associated genes, a ribonuclease protection assay was performed for fibroblasts exposed to anti‐Fas antibody and tumor necrosis factor‐α to activate the Fas/TNF receptor apoptotic pathway. Compared with normal skin fibroblasts, keloid fibroblasts exhibited decreased expression of apoptosis‐associated genes.