PC4在小鼠皮肤伤口愈合过程中起到负调控作用。
PC4 serves as a negative regulator of skin wound healing in mice.
作者信息
Liao Fengying, Chen Long, Luo Peng, Jiang Zhongyong, Chen Zelin, Wang Ziwen, Zhang Chi, Wang Yu, He Jintao, Wang Qing, Wang Yawei, Liu Lang, Huang Yu, Wang Huilan, Jiang Qingzhi, Luo Min, Gan Yibo, Liu Yunsheng, Wang Yang, Wu Jie, Xie Wentao, Cheng Zhuo, Dai Yali, Li Jialun, Liu Zujuan, Yang Fan, Shi Chunmeng
机构信息
Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Institute of Clinical Medicine, Southwest Medical University, 646000 Luzhou, China.
出版信息
Burns Trauma. 2020 May 5;8:tkaa010. doi: 10.1093/burnst/tkaa010. eCollection 2020.
BACKGROUND
Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model.
METHODS
A PC4 knock-in mouse model (PC4) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay.
RESULTS
The PC4 mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4 skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4 mice .
CONCLUSIONS
This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.
背景
人正向辅因子4（PC4）最初被表征为一种多功能转录辅因子，但其在皮肤伤口愈合中的作用仍不清楚。本研究的目的是通过PC4基因敲入小鼠模型探讨PC4在皮肤伤口愈合中的作用。
方法
使用具有背部全层伤口的PC4基因敲入小鼠模型（PC4）来研究PC4在皮肤伤口愈合中的生物学功能。进行定量PCR、蛋白质印迹分析和免疫组织化学以评估PC4的表达；进行天狼星红染色和免疫荧光以探究胶原沉积和血管生成的变化。使用Ki67染色和TUNEL检测法检测增殖和凋亡。从小鼠皮肤中分离出原代真皮成纤维细胞以进行细胞划痕实验、cck-8检测和集落形成检测。
结果
PC4小鼠可育，未表现出明显异常，但背部皮肤的皮肤愈合明显延迟。组织学染色显示PC4皮肤中再上皮化不足、血管生成减少和胶原沉积减少、凋亡增加以及细胞增殖减少。我们的数据还显示，来自PC4小鼠的培养原代成纤维细胞的迁移率和增殖能力降低。
结论
本研究表明PC4可能是小鼠皮肤伤口愈合的负调节因子。
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