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High Expression of SERPINE1 and CTSL in Keratinocytes in Pressure Injury Caused by Ischemia-reperfusion Injury

ABSTRACT: 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 the key to developing effective prevention and therapeutic strategies. 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 ischemic-reperfusion (I/R) injury from GeneCards database to analyze and screen prognostic related target genes. There were finally 7 candidate genes obtained from the intersection of the three datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (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 assessed using the nomogram and Receiver Operating Characteristic (ROC) approaches, and the findings indicated that these two genes had a high prognosis value. The two genes 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. According to our research we referred that the SERPINE1 and CTSL might be the potential biomarkers of PI.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE279186 | GEO | 2025/01/16

REPOSITORIES: GEO

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Project description:# Background Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI. # Methods Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing. # Results CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat, Serpine1, Thbd, Icam1, Stat3, and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation. # Conclusion Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI.

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High Expression of SERPINE1 and CTSL in Keratinocytes in Pressure Injury Caused by Ischemia-reperfusion Injury

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