Effect of Camptothecin on Collagen Synthesis in Fibroblasts From Patients With Keloid
Effect of Camptothecin on Collagen Synthesis in Fibroblasts From Patients With Keloid
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DOI：
10.1097/sap.0b013e3181872775
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发表时间：
2009-07
影响因子：
1.5
通讯作者：
Guo‐You Zhang;Weiyang Gao;Xuan Li;C. Yi;Yan Zheng;Yang Li-;B. Xiao;Xianjie Ma;Li Yan;K. Lu;Yan Han;Shu-zhong Guo
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文献类型：
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作者：
Guo‐You Zhang;Weiyang Gao;Xuan Li;C. Yi;Yan Zheng;Yang Li-;B. Xiao;Xianjie Ma;Li Yan;K. Lu;Yan Han;Shu-zhong Guo
疤痕疙瘩的特点是真皮中胶原蛋白大量沉积，导致细胞外基质的产生和聚集不平衡。本研究旨在评估拓扑异构酶 I 抑制剂喜树碱 (CPT) 对健康供体和疤痕疙瘩患者的活化真皮成纤维细胞中胶原蛋白合成的影响。在存在或不存在 CPT 的情况下培养成纤维细胞。通过MTT分析确定细胞毒性测定。使用常规定量实时逆转录 PCR 和蛋白质印迹在转录和转录后水平研究 I 型胶原和 III 型胶原的表达。结果表明，瘢痕疙瘩成纤维细胞中胶原蛋白 1（而不是胶原蛋白 3）的合成主要出现明显的剂量依赖性减少，且没有明显的细胞毒性。 CPT通过抑制I型胶原蛋白的分泌，对瘢痕疙瘩成纤维细胞代谢中I/III型胶原蛋白的比例具有调节作用。数据表明，CPT（一种拓扑异构酶 I 抑制剂）对胶原蛋白合成的抑制作用可能是限制瘢痕疙瘩患者纤维化的有效治疗方法。
Keloids are distinguished by substantial deposition of collagen in the dermis, resulting in an imbalanced production and aggregation of extra cellular matrix. This study was undertaken to evaluate the effects of the topoisomerase I inhibitor camptothecin (CPT) on collagen synthesis in the activated dermal fibroblasts from healthy donors and patients with keloid. The fibroblasts were cultured in the presence or absence of CPT. Cellular toxicity assay was determined by MTT analysis. The expression of type I collagen and type III collagen was studied both at the transcriptional and post-transcriptional levels, using conventional quantitative real-time reverse transcription PCR and Western blotting. Results showed that there was predominantly a clear and dose-dependent decrease in the synthesis of collagen 1, not collagen 3, in keloid fibroblasts without significantly cellular toxicity. The CPT had an activity on the regulation of the ratio of type I/III collagen in the metabolism of keloid fibroblasts by inhibiting the secretion of type I collagen. The data suggest that the inhibitory effect of CPT, a topoisomerase I inhibitor, on collagen synthesis may be an effective treatment for limiting fibrosis in keloid patients.