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牛皮癣素(S100A7)对人类伤口愈合的分子和细胞影响。

Molecular and cellular impact of Psoriasin (S100A7) on the healing of human wounds.

作者信息

Rangaraj Aravindan, Ye Lin, Sanders Andrew James, Price Patricia Elaine, Harding Keith Gordon, Jiang Wen Guo

机构信息

Cardiff China Medical Research Collaborative, Institute of Cancer and Genetics, Cardiff University School of Medicine, CF14 4XN Cardiff, UK.

Department of Wound Healing, Cardiff University School of Medicine, CF14 4XN Cardiff, UK.

出版信息

Exp Ther Med. 2017 May;13(5):2151-2160. doi: 10.3892/etm.2017.4275. Epub 2017 Mar 28.

Abstract

Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium-responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte function and differentiation during wound healing. The aim of the present study was to determine the cellular impact of Psoriasin in keratinocytes, which are the primary cell type associated with wound healing. Psoriasin expression in wound tissues was examined using reverse transcription-quantitative polymerase chain reaction and immunochemical staining. Knockdown of Psoriasin in HaCaT cells was performed using anti-Psoriasin ribozyme transgenes and the effect on growth, adhesion and migration of keratinocytes was subsequently determined using cellular functional assays. Psoriasin expression is upregulated in wounds, particularly at the wound edges. The present study demonstrated that Psoriasin is expressed in keratinocytes and is a fundamental regulator of keratinocyte migration. Significant increases in the rate of keratinocyte adhesion, migration and growth were observed in Psoriasin-deficient cells (P<0.01 vs. control). Application of small inhibitors identified the potential association of neural Wiskott-Aldrich syndrome protein, focal adhesion primase and rho-associated protein kinase signalling pathways with Psoriasin-regulated cell adhesion and motility. In conclusion, Psoriasin serves an important role in the wound healing process, suggesting that it may be utilized as a potential wound healing biomarker.

摘要

银屑素,也被称为S100A7,是S100蛋白家族的成员,该家族是一组钙反应信号蛋白。银屑素在银屑病患者中表达仍然很高,而在浸润性乳腺癌患者中表达下调。这一观察结果表明,这种蛋白质可能是伤口愈合过程中角质形成细胞功能和分化的一个显著标志物。本研究的目的是确定银屑素对角质形成细胞的细胞影响,角质形成细胞是与伤口愈合相关的主要细胞类型。使用逆转录定量聚合酶链反应和免疫化学染色检测伤口组织中银屑素的表达。使用抗银屑素核酶转基因在HaCaT细胞中敲低银屑素,随后使用细胞功能测定法确定对角质形成细胞生长、粘附和迁移的影响。银屑素在伤口中表达上调,尤其是在伤口边缘。本研究表明,银屑素在角质形成细胞中表达,是角质形成细胞迁移的基本调节因子。在缺乏银屑素的细胞中观察到角质形成细胞粘附、迁移和生长速率显著增加(与对照组相比,P<0.01)。应用小分子抑制剂确定了神经维斯科特-奥尔德里奇综合征蛋白、粘着斑引物酶和rho相关蛋白激酶信号通路与银屑素调节的细胞粘附和运动的潜在关联。总之,银屑素在伤口愈合过程中起重要作用,表明它可能被用作潜在的伤口愈合生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4703/5443246/b08290ab4996/etm-13-05-2151-g00.jpg

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