Anti-PLAU monoclonal antibody, clone V-27

OBJECTIVES: Severe sepsis after trauma still associated with a high mortality rate in intensive care units (ICU). In this study we aimed to identify genes related to multiple trauma complicated by severe sepsis. MATERIALS AND METHODS: The gene expression profile dataset GSE12624 including 36 samples of traumatic patients not complicated by sepsis and 34 traumatic patients complicated by sepsis was downloaded from GEO (Gene Expression Omnibus) database. The limma package in R was applied to identify differentially expressed genes (DEGs) between these two groups of samples. All the DEGs were divided into up- and down-regulation groups according to the changes of their expression value, which were then subjected to GO enrichment analysis. Two genes with largest changes among the up- and down-regulation groups were selected. Interaction networks based on these two genes were constructed using HitPredict software and then pathway enrichment analysis for the networks were performed by WebGestalt software. RESULTS: A total of 21 up-regulated genes and 37 down-regulated genes were obtained, which were mainly related to GO terms "endopeptidase inhibitor activity" and "response to wounding", respectively. The vertical bar logFC vertical bar of genes PLAU (urokinase-type plasminogen activator) and MMP8 (matrix metalloproteinase-8) ranked first in down-regulated or up-regulated list. There were 18 genes which can interact with PLAU at a high degree of confidence while there were 5 genes with MMP8. Further analysis showed that PLAU was closely associated with the pathway "complement and coagulation cascades". CONCLUSIONS: PLAU and MMP8 may act as potential targets for diagnosis and therapy of trauma complicated by sepsis.

It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-kappa B in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-kappa B in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration. Consistently, depletion or inactivation of Notch1 resulted in decreased filopodia formation, increased focal adhesion and actin stress fiber, leading to reduced keratinocyte migration and skin wound healing. Thus, our findings provide the molecular mechanism involving JMJD3/NF-kappa B-Notch pathway in keratinocyte wound healing.