Dynamics of Short-Term Gene Expression Profiling in Liver Following Thermal Injury

Abstract

Background Severe trauma, including burns, triggers a systemic response that significantly impacts on the liver, which plays a key role in the metabolic and immune responses aimed at restoring homeostasis. While many of these changes are likely regulated at the gene expression level, there is a need to better understand the dynamics and expression patterns of burn injury-induced genes in order to identify potential regulatory targets in the liver. Herein we characterized the response within the first 24 h in a standard animal model of burn injury using a time series of microarray gene expression data. Methods Rats were subjected to a full thickness dorsal scald burn injury covering 20% of their total body surface area while under general anesthesia. Animals were saline resuscitated and sacrificed at defined time points (0, 2, 4, 8, 16, and 24 h). Liver tissues were explanted and analyzed for their gene expression profiles using microarray technology. Sham controls consisted of animals handled similarly but not burned. After identifying differentially expressed probesets between sham and burn conditions over time, the concatenated data sets corresponding to these differentially expressed probesets in burn and sham groups were combined and analyzed using a “consensus clustering” approach. Results The clustering method of expression data identified 621 burn-responsive probesets in 4 different co-expressed clusters. Functional characterization revealed that these 4 clusters are mainly associated with pro-inflammatory response, anti-inflammatory response, lipid biosynthesis, and insulin-regulated metabolism. Cluster 1 pro-inflammatory response is rapidly up-regulated (within the first 2 h) following burn injury, while Cluster 2 anti-inflammatory response is activated later on (around 8 h post burn). Cluster 3 lipid biosynthesis is downregulated rapidly following burn, possibly indicating a shift in the utilization of energy sources to produce acute phase proteins which serve the anti-inflammatory response. Cluster 4 insulin-regulated metabolism was down-regulated late in the observation window (around 16 h postburn), which suggests a potential mechanism to explain the onset of hypermetabolism, a delayed but well-known response that is characteristic of severe burns and trauma with potential adverse outcome. Conclusions Simultaneous analysis and comparison of gene expression profiles for both burn and sham control groups provided a more accurate estimation of the activation time, expression patterns, and characteristics of a certain burn-induced response based on which the cause-effect relationship among responses were revealed.

Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

“…In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al, 2012 [1,4] ; Mattick et al 2012, 2013 [2,3] ; Nguyen et al, 2014 [5] ; Orman et al, 2011, 2012 [6–8] ).…”

Effects of Scald Injuries on Liver and Brain Adult Male Albino Rats (Biochemical, Histopathological and Immunohistochemical Study)

“…Clinical studies have shown that an uncontrolled and prolonged action of inflammatory cytokines, which is evidenced by a sustained release of acute phase proteins, may contribute to detrimental complications after thermal injury (Yang et al, 2012).…”

Keratinocyte growth factor and the expression of wound-healing-related genes in primary human keratinocytes from burn patients

“…In the first 24 to 48 hours after an injury, a progressive deepening of wound takes place 11 . In the following days, extensive changes in gene expression of woundhealing-related cells may result in impaired re-epithelialization 12,13 .…”