Gene expression profiles of livers from thermally injured rats

Dasu, Mohan R.; Cobb, J. Perren; Laramie, Jason M.; Chung, Tae-Hoon; Spies, Marcus; Barrow, Robert E.

doi:10.1016/j.gene.2003.11.015

Cited by 29 publications

(25 citation statements)

References 29 publications

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“…However, Nas1 Ϫ/Ϫ mice showed no evidence of liver inflammation in hematoxylin-and eosin-stained sections (16), suggesting an injury in extrahepatic tissues. During acute stress, hepatocyte proliferation and steatosis is stimulated (15), which is consistent with our findings of hepatomegaly (16) and fatty liver (Fig. 2) in Nas1 Ϫ/Ϫ mice.…”

Section: Nas1supporting

confidence: 92%

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Dawson

Gardiner

Grimmond

et al. 2006

Physiological Genomics

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. Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice. Physiol Genomics 26: 116 -124, 2006. First published April 18, 2006 doi:10.1152/physiolgenomics.00300.2005.-Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na ϩ -SO 4 2Ϫ cotransporter, NaS1. We previously generated a NaS1 knockout (Nas1 Ϫ/Ϫ ) mouse, an animal model for hyposulfatemia, that exhibits reduced growth and liver abnormalities including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Nas1 Ϫ/Ϫ mice using oligonucleotide microarrays. The mRNA expression levels of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription, or protein synthesis were increased (n ϭ 51) or decreased (n ϭ 41) in Nas1 Ϫ/Ϫ mice when compared with Nas1 ϩ/ϩ mice. The most upregulated transcript levels in Nas1 Ϫ/Ϫ mice were found for the sulfotransferase genes, Sult3a1 (Ϸ500% increase) and Sult2a2 (100% increase), whereas the metallothionein-1 gene, Mt1, was among the most downregulated genes (70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1, and Apoa4, were found to be upregulated (Ն30% increase) in Nas1 Ϫ/Ϫ mice. In addition, Nas1 Ϫ/Ϫ mice exhibited increased levels of hepatic lipid (Ϸ16% increase), serum cholesterol (Ϸ20% increase), and low-density lipoprotein (Ϸ100% increase) and reduced hepatic glycogen (Ϸ50% decrease) levels. In conclusion, these data suggest an altered lipid and cholesterol metabolism in the hyposulfatemic Nas1 Ϫ/Ϫ mouse and provide new insights into the metabolic state of the liver in Nas1 Ϫ/Ϫ mice.

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Section: Nas1supporting

confidence: 92%

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Dawson

Gardiner

Grimmond

et al. 2006

Physiological Genomics

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“…While significant strides have been made in the systems-based profiling of patients with global inflammatory states (such as the work done within the context of the Inflammation and Host Response to Injury "Glue Grant"; www.gluegrant.org), [53][54][55][56][57][58][59][60] there is still a need for a mechanistic means of translating basic science knowledge to global behavior. With this exigency in mind, the initial TSB models focused on conceptually characterizing the global dynamics of sepsis using models based on the "best" mechanistic knowledge available.…”

Section: Application Of Tsb To Sepsis: a Test Casementioning

confidence: 99%

“…Furthermore, the development of multiple TSB models of the acute response to burn injury and resuscitation might provide a means of rational, biologically mechanistic analysis of the genomic information generated by large-scale programs such as the Inflammation and Host Response to Injury "Glue Grant." [53][54][55][56][57][58][59][60] In this fashion TSB could provide a translational bridge between data on gene regulatory mechanisms and the clinical setting. TSB has already taken steps in this direction by linking hepatic transcriptome data to injury and hemorrhagic shock in a dynamic mathematical model 31 .…”

Section: Resuscitation Issuesmentioning

confidence: 99%

“…For the former, one goal would be to have a readily available means for molecular fingerprinting of the response of the lung to injury in a fashion that is predictive of disease course and outcome. As mentioned above, efforts of projects such as the Inflammation and Host Response to Injury "Glue Grant" [53][54][55][56][57][58][59][60] provide invaluable information regarding the link between the genetic and genomic profile and the physiologic state of these types of patients, and are paving the road to being able to "personalize" medical therapy. However, the goal of "personalizing" diagnosis and care requires a substantial evolution in how these data are used.…”

Section: Inhalation Injurymentioning

confidence: 99%

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Translational Systems Biology: Introduction of an Engineering Approach to the Pathophysiology of the Burn Patient

Faeder

Vodovotz

2008

Journal of Burn Care & Research

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The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research. BURNS, BIOCOMPLEXITY, AND THE NEED FOR A TRANSLATIONAL METHODOLOGYThe burn community held its State of the Science meeting (Sponsored by the American Burn Association, the National Institutes of Health/National Institute of General Medical Sciences, the Shriners Hospitals for Children, the National Institute on Disability and Rehabilitation Research, the Department of Veterans Affairs and the U.S. Army Medical Materiel Command) from October 26-29, 2006, in order to determine the areas and foci of the community's research emphasis for the decade to come. These areas were defined primarily by their clinical manifestations or situations, such as resuscitation issues, inhalation injury, multiple organ failure, and wound healing. However, discussions invariably included references to the investigation of means by which known or suspected cellular and molecular pathophysiologic mechanisms could be translated into effective clinical treatments. These discussions included both the process of discovery for new

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“…Thermal burn injuries to the skin may respond with inflammation, cellular protection mechanisms, immune suppression, hypermetabolic dysfunction or organs [6,7]. Pain may be due to skin inflammation, along with the appearance of exudate and cytokine production such as tumor necrosis factor (TNF)-α and interleukins (IL) such as IL-6, IL-8 and IL-10 [8,9].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of low-level laser in burn wound models in rats

Kim

2017

PTRS

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Objective: The anti-inflammatory effects of low-level laser in burn wound model in rats were investigated. Design: Randomized controlled trial. Methods: The rats were assigned to three experimental groups. Group I received second-degree burn wounds; Group II received dressing film and low-level laser (1.2 J/cm 2 ) treatment after a burn wound; Group III received dressing film and low-level laser (2.3 J/cm 2 ) treatment after a burn wound. After inducing a deep second-degree burn wound, the wound was observed every day and the burn area diameter and retraction quantification at 1, 7, and 14 days were evaluated. Low-level laser was investigated on hematological parameters after 14 days. Effects of low-level laser on the inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]) concentrations in the serum were evaluated using immunosorbent assay kits. Results: Group III showed a significant difference in wound size on days 7 and 14 compared to Group I (p<0.05). Group II showed a significant difference in wound size on day 14 compared to Group I (p<0.05). For wound contraction percentage, both laser therapy treatment groups showed a significant difference compared with Group I (p<0.05). There was also a significant difference in wound contraction percentage in Group III compared to Group II (p<0.05). Compared with the model control group, decreased TNF-α and IL-6 levels in the serum was observed at 14 days after burn wound induction. Conclusions:The results of this study suggest that low-level laser therapy can assist in burn wound healing, which might be associated with decreased concentrations of TNF-α and IL-6 related proinflammatory cytokines.

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Gene expression profiles of livers from thermally injured rats

Cited by 29 publications

References 29 publications

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Translational Systems Biology: Introduction of an Engineering Approach to the Pathophysiology of the Burn Patient

Anti-inflammatory effects of low-level laser in burn wound models in rats

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