Suppressor of Fused Inhibits Skin Wound Healing

Suppressor of Fused Inhibits Skin Wound Healing
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融合抑制剂抑制皮肤伤口愈合

DOI:
10.1089/wound.2018.0890
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发表时间:
2020
影响因子:
4.9
通讯作者:
Xiao-Yong Man
Xiao-Yong Man
中科院分区:
医学3区
文献类型:
--
作者:
Bei-Bei Yang;Yu-Xin Zheng;Bing-Xi Yan;Hua-Li Cao;Lilla L;eck;Jia-Qi Chen;Wei Li;Min Min;Ping Wang;Sui-Qing Cai;Min Zheng;Xiao-Yong Man

文献摘要

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目的:探讨融合抑制因子(Sufu)对表皮和真皮细胞特性及伤口愈合的影响。方法:采用表皮过表达人Sufu(hSufu)的转基因(TG)小鼠,研究Sufu对表皮和真皮细胞特性及伤口愈合的影响。TG小鼠表现出显著延迟的皮肤伤口愈合。此外,K14-hSufuTG小鼠中培养的角质形成细胞的迁移和增殖能力降低。转化生长因子-β处理增加WT中α-平滑肌肌动蛋白的表达多于TG成纤维细胞。与对照组相比,K14-hSufu TG小鼠伤口中的β-catenin、胶质瘤转录因子1(Gli 1)和基质金属蛋白酶-3的表达显著降低,这可能表明Sufu通过阻断hedgehog(Hh)/Gli和Wnt/β-catenin通路而延迟伤口愈合。创新:我们的研究结果表明Sufu在皮肤伤口愈合过程中的一个新特性。结论:Sufu在表皮中的过表达可能通过抑制Hh/Gli和Wnt/β-catenin信号通路而影响创面愈合。这些数据为进一步分析腐乳在皮肤创伤愈合中的作用提供了重要依据。
Objectives:To investigate the effect of suppressor of fused (Sufu) on epidermal and dermal cellular properties and in wound healing.Approach:Transgenic (TG) mice overexpressing human Sufu (hSufu) in the epidermis were applied to investigate the effects of Sufu on epidermal and dermal cellular properties and in wound healing.Results:Histological staining revealed a reduction of epidermal and dermal thickness and an increase of hypodermal adipose tissue in homozygous K14-hSufu TG mice when compared with wild-type (WT) controls. TG mice exhibited significantly delayed skin wound healing. Moreover, the migratory and proliferative capabilities of cultured keratinocytes were decreased in K14-hSufuTG mice. Transforming growth factor-β treatment increased the expression of α-smooth muscle actin more in WT than in TG fibroblasts. Sufu overexpression significantly decreased the expression of β-catenin, glioma transcription factor 1 (Gli1), and matrix metalloproteinase-3 in wounds of K14-hSufu TG mice when compared with controls, probably indicating a delaying effect of Sufu on wound healing via blocking the hedgehog (Hh)/Gli and Wnt/β-catenin pathway.Innovation:Our results indicate a new property of Sufu in the process of skin wound healing. It provides an important basis for Sufu as a potential target for skin wound healing.Conclusion:Our findings suggest that Sufu overexpression in the epidermis impairs wound healing via dampening the Hh/Gli and Wnt/β-catenin signaling pathway. These data provide an important basis for further analyses of Sufu in skin wound healing.