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肥厚性瘢痕和瘢痕疙瘩与正常皮肤差异分析中涉及的生物标志物的鉴定。

Identification of biomarkers involved in differential profiling of hypertrophic and keloid scars versus normal skin.

作者信息

Suarez Edna, Syed Farhatullah, Alonso-Rasgado Teresa, Bayat Ardeshir

机构信息

Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology (MIB), University of Manchester, 131 Princess Road, Manchester, M1 7ND, UK.

出版信息

Arch Dermatol Res. 2015 Mar;307(2):115-33. doi: 10.1007/s00403-014-1512-4. Epub 2014 Oct 17.

Abstract

Among raised dermal scar types, keloid (KS) and hypertrophic scars (HS) are considered to present clinical similarities, but there are no known specific biomarkers that allow both scar types to be easily distinguished. Development and progression of raised dermal scars comprises the activation of several molecular pathways and cell defence mechanisms leading to elevated extracellular matrix component synthesis, delayed apoptosis, altered migration and differentiation. Therefore, the aim here was to identify biomarkers that may differentiate between KS and HS compared to normal skin (NS). To achieve this aim, NS (n = 14), KS (n = 14) and HS (n = 14) biopsies were evaluated using histology by H&E staining. Tissue biopsies and primary fibroblasts (passages 0-4) were employed to assess the gene expression levels of 21 biomarkers selected from our previous microarray studies using qRT-PCR. Finally, protein expression was evaluated using In-Cell Western Blotting in primary fibroblasts (p 0-4). Our results demonstrated that out of the 21 biomarkers screened at mRNA and protein levels, α2β1-integrin, Hsp27, PAI-2, MMP-19 and CGRP showed significantly higher expression (p < 0.05) in KS compared to NS and HS. Additionally, these five key biomarkers were found to be significantly higher (p < 0.05) at mRNA level in KS taken from the sternum, a region known to be subjected to high mechanical forces in the body during the performance of daily movements. In conclusion, our findings offer potential molecular targets in raised dermal scars differentiation. Future targeted research may allow provision of diagnostic and prognostic markers in keloid versus hypertrophic scars.

摘要

在增生性皮肤瘢痕类型中,瘢痕疙瘩(KS)和增生性瘢痕(HS)被认为具有临床相似性,但目前尚无已知的特异性生物标志物能够轻易区分这两种瘢痕类型。增生性皮肤瘢痕的发生和发展涉及多种分子途径和细胞防御机制的激活,导致细胞外基质成分合成增加、细胞凋亡延迟、迁移和分化改变。因此,本研究的目的是识别与正常皮肤(NS)相比,可能区分KS和HS的生物标志物。为实现这一目标,我们对NS(n = 14)、KS(n = 14)和HS(n = 14)的活检组织进行苏木精-伊红(H&E)染色的组织学评估。使用组织活检和原代成纤维细胞(第0 - 4代),通过定量逆转录聚合酶链反应(qRT-PCR)评估从我们之前的微阵列研究中选择的21种生物标志物的基因表达水平。最后,在原代成纤维细胞(第0 - 4代)中使用细胞内蛋白质印迹法评估蛋白质表达。我们的结果表明,在mRNA和蛋白质水平筛选的21种生物标志物中,α2β1整合素、热休克蛋白27(Hsp27)、纤溶酶原激活物抑制剂-2(PAI-2)、基质金属蛋白酶-19(MMP-19)和降钙素基因相关肽(CGRP)在KS中的表达明显高于NS和HS(p < 0.05)。此外,在取自胸骨的KS中,这五个关键生物标志物在mRNA水平上也明显更高(p < 0.05),胸骨是身体在日常活动中承受高机械力的区域。总之,我们的研究结果为增生性皮肤瘢痕的鉴别提供了潜在的分子靶点。未来的靶向研究可能有助于提供瘢痕疙瘩与增生性瘢痕的诊断和预后标志物。

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