High expression of SERPINE1 and CTSL in keratinocytes in pressure injury caused by ischemia-reperfusion injury

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2025-04-01 Epub Date: 2025-01-22 DOI:10.1016/j.tice.2025.102746

Lexuan Bi , Yaxin Liu , Lei Zhang , Xiaoli Zhang , Dong Wang

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引用次数: 0

Abstract

Introduction

Pressure Injury (PI) is a complex disease process which is influenced by multiple factors, among which ischemia-reperfusion (I/R) injury is closely related to the progression of PI. But its biomarkers are still unclearly. Understanding its physiological mechanisms and related molecular biomarkers is a key to developing effective prevention and therapeutic strategies.

Methods

This study through obtained the candidate genes of the differentially expressed genes (DEGs) from the PI rat model by transcriptome sequencing, PI single-cell sequencing database, and genes related to I/R injury from GeneCards database to analyze and screen prognostic related target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway analysis were performed using clusterProfiler package, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The genes related to I/R injury were identified and analyzed using three machine learning algorithms. Then, the hub genes were evaluated using nomogram and receiver operating characteristic (ROC) curves, and validated using immunohistochemistry in the PI rat model.

Results

There were finally 7 candidate genes obtained from the intersection of the three datasets. GO and KEGG pathway analysis revealed that the DEGs were enriched in complement and coagulation cascades, and the keratinocyte differentiation is a significant factor. Then, two hub genes Serine protease inhibitor clade E member 1 (SERPINE1) and Cathepsin L (CTSL) were identified through three machine learning algorithms. The two hub genes were indicated had a high prognosis value by nomogram and ROC curves. SERPINE1 and CTSL both play crucial roles in vasculogenesis, coagulation and degradation of the extracellular matrix, which is essential for wound healing. The results of immunohistochemistry demonstrated that SERPINE1 and CTSL are significantly upregulated in skin tissue from PI caused by I/R injury, and their mRNA expression levels significantly correlate with PI outcomes.

Conclusion

According to our research we referred that the SERPINE1 and CTSL might be the potential biomarkers of PI.

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SERPINE1和CTSL在缺血再灌注应激性损伤的角质形成细胞中高表达。

压力性损伤（PI）是一个复杂的疾病过程，受多种因素影响，其中缺血再灌注（I/R）损伤与PI的进展密切相关。但其生物标志物仍不清楚。了解其生理机制和相关分子生物标志物是制定有效预防和治疗策略的关键。方法：本研究通过转录组测序、PI单细胞测序数据库、GeneCards数据库中I/R损伤相关基因获取PI大鼠模型中差异表达基因（DEGs）候选基因，分析筛选预后相关靶基因。利用clusterProfiler软件包进行基因本体（GO）和京都基因组百科全书（KEGG）通路分析，并构建蛋白-蛋白相互作用（PPI）网络识别枢纽基因。使用三种机器学习算法识别和分析与I/R损伤相关的基因。然后，使用nomogram和receiver operating characteristic （ROC）曲线评估中枢基因，并在PI大鼠模型中使用免疫组织化学进行验证。结果：三个数据集的交集最终得到7个候选基因。GO和KEGG通路分析显示，DEGs在补体和凝血级联中富集，角质细胞分化是一个重要因素。然后，通过三种机器学习算法鉴定出两个中心基因丝氨酸蛋白酶抑制剂进化枝E成员1 （SERPINE1）和组织蛋白酶L （CTSL）。两种中心基因均具有较高的预后价值。SERPINE1和CTSL在血管生成、凝血和细胞外基质降解中都起着至关重要的作用，这对伤口愈合至关重要。免疫组化结果显示，I/R损伤后PI皮肤组织中SERPINE1和CTSL表达显著上调，且其mRNA表达水平与PI预后显著相关。结论：根据我们的研究，SERPINE1和CTSL可能是PI的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.