Gene Expression Profiling of Long-Term Changes in Rat Liver Following Burn Injury

Abstract

The inflammatory response initiated upon burn injury is also associated with extensive metabolic adjustments. While there is a significant body of literature on the characterization of these changes at the metabolite level, little is known on the mechanisms of induction, especially with respect to the role of gene expression. We have comprehensively analyzed changes in gene expression in rat livers during the first 7 d after 20% total body surface area burn injury using Affymetrix microarrays. A total of 740 genes were significantly altered in expression at 1, 2, 4, and 7 d after burn injury compared to sham-burn controls. Functional classification based on gene ontology terms indicated that metabolism, transport, signaling, and defense/inflammation response accounted for more than 70% of the significantly altered genes. Fisher least-significant difference post-hoc testing of the 740 differentially expressed genes indicated that over 60% of the genes demonstrated significant changes in expression either on d 1 or on d 7 postburn. The gene expression trends were corroborated by biochemical measurements of triglycerides and fatty acids 24 h postburn but not at later time points. This suggests that fatty acids are used, at least in part, in the liver as energy substrates for the first 4 d after injury. Our data also suggest that long-term regulation of energy substrate utilization in the liver following burn injury is primarily at the posttranscriptional level. Last, relevance networks of significantly expressed genes indicate the involvement of key small molecules in the hepatic response to 20% total body surface area burn injury.

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

“…This model was chosen because it has nearly 100% long-term survival, no evidence of systemic hypoperfusion, and no significant alterations on feeding patterns (13). Rats were first randomized into two groups: burn and sham burn (control group).…”

“…Recently, microarray technology and transcriptional profiling have been used to elucidate genome-wide changes in the liver following the burn injury (1, 3, 13). Vemula and co-workers (3) analyzed gene expression changes in rat livers during the first 24 h following the burn injury.…”

The dynamics of the early inflammatory response in double-hit burn and sepsis animal models

“…Rats first received a full-thickness burn on an area of the dorsal skin corresponding to 20% of the total body surface area (TBSA). This model has nearly 100% long-term survival, no evidence of systemic hypoperfusion, and no significant effect on feeding pattern [28-30]. Rats were anesthetized by intraperitoneal injection of 80 to 100 mg/kg ketamine + 12 to 10 mg/kg xylazine, and all hair removed from the dorsal abdominal area using electric clippers.…”

A time course study about gene expression of post‐thermal injury with DNA microarray

“…With the support of gene chip technology, we are able to observe global changes and thus elucidate molecular mechanisms . By now, a range of studies have been carried out focusing on burn injuries with this technology . However, currently available knowledge is not enough for clinical treatments.…”