Identification of potential markers of fatal hypothermia by a body temperature-dependent gene expression assay.
Animals
Body Temperature
Connective Tissue Growth Factor
/ genetics
Gene Expression
Genetic Markers
Hemorrhage
/ pathology
Hypothermia
/ diagnosis
Immunohistochemistry
Models, Animal
Muscle, Skeletal
/ metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1
/ genetics
RNA, Messenger
/ metabolism
Rats, Wistar
Sequence Analysis, DNA
/ methods
Syndecan-4
/ genetics
Thermogenesis
/ genetics
Transcription Factors
/ genetics
Up-Regulation
Body temperature-dependent gene expression analysis
Iliopsoas muscle
Marker gene
Thermogenesis
Journal
International journal of legal medicine
ISSN: 1437-1596
Titre abrégé: Int J Legal Med
Pays: Germany
ID NLM: 9101456
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
06
04
2018
accepted:
22
06
2018
pubmed:
1
7
2018
medline:
4
4
2019
entrez:
1
7
2018
Statut:
ppublish
Résumé
Diagnosis of fatal hypothermia is considered to be difficult in forensic practice and even if findings due to cold exposure are evident, cold exposure is not necessarily a direct cause of death. Identification of useful molecular markers for the diagnosis of fatal hypothermia has not been successful. In this study, to identify novel molecular markers that inform the diagnosis of fatal hypothermia, we focused on skeletal muscle, which plays a role in cold-induced thermogenesis in mammals. We made rat models of mild, moderate, and severe hypothermia and performed body temperature-dependent gene expression analysis in the iliopsoas muscle using next-generation sequencing (NGS). NGS showed that after severe hypothermia, the expression levels of 91 mRNAs were more than double those in mild and moderate hypothermia and control animals. Gene ontology (GO) analysis indicated that these mRNAs are involved in a number of biological processes, including response to stress and lipids, and cellular response to hypoxia. The expression of four genes [connective tissue growth factor (Ctgf), JunB proto-oncogene, AP-1 transcription factor subunit (Junb), nuclear receptor subfamily 4, group A, member 1 (Nr4a1), and Syndecan 4 (Sdc4)] and the level of one protein (CTGF) were induced only by severe hypothermia. These genes and protein are involved in muscle regeneration, tissue repair, and lipid metabolism. These results indicate that heat production to maintain body temperature in a process leading to fatal hypothermia might be performed by the iliopsoas muscle, and that Ctgf, Junb, Nr4a1, and Sdc4 genes are potential diagnostic markers for fatal hypothermia.
Identifiants
pubmed: 29959558
doi: 10.1007/s00414-018-1888-3
pii: 10.1007/s00414-018-1888-3
doi:
Substances chimiques
CCN2 protein, rat
0
Genetic Markers
0
JunB protein, mouse
0
Nr4a1 protein, rat
0
Nuclear Receptor Subfamily 4, Group A, Member 1
0
RNA, Messenger
0
Sdc4 protein, rat
0
Syndecan-4
0
Transcription Factors
0
Connective Tissue Growth Factor
139568-91-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-345Subventions
Organisme : Japan Society for the Promotion of Science
ID : 16K09210
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