IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture

Autor: Gabriel A. Aguirre, LA Morales, R. G. de la Garza, Mariano García-Magariño, Inma Castilla-Cortázar, Irene Martín-Estal, Víctor Javier Lara-Díaz, Juan E. Puche, Úrsula Muñoz
Rok vydání: 2017
Předmět:
tight junction protein
Male
0301 basic medicine
Physiology
Biochemistry
Cell junction
murine model
Hepatitis
immunology
Extracellular matrix
Mice
Gene expression
animal
genetics
cytoskeleton protein
Insulin-Like Growth Factor I
somatomedin receptor
Receptor
Cytoskeleton
comparative study
liver tissue
Extracellular Matrix Proteins
Tight junction
messenger RNA
acute phase protein
liver structure
scleroprotein
igf1 gene
Desmosomes
General Medicine
protein function
Cadherins
Cell biology
cell polarity
medicine.anatomical_structure
Liver
Hepatocyte
IGF-1
Original Article
wild type
Inflammation Mediators
medicine.symptom
autacoid
gene overexpression
Injections
Subcutaneous

animal experiment
Mice
Transgenic

Inflammation
protein deficiency
Biology
subcutaneous drug administration
Article
animal tissue
histology
reverse transcription polymerase chain reaction
03 medical and health sciences
lipid
acute phase response
medicine
heterozygosity
cross breeding
Animals
controlled study
Tight junctions
mouse
Crosses
Genetic

nonhuman
Tight Junction Proteins
Gene Expression Profiling
Receptors
Somatomedin

somatomedin C
insulin-like growth factor-1
mouse

Molecular biology
cell junction
transgenic mouse
Cytoskeletal Proteins
Oxidative Stress
cadherin
030104 developmental biology
7 INGENIERÍA Y TECNOLOGÍA
Gene Expression Regulation
inflammation
protein analysis
protein blood level
Hepatocytes
pathology
microarray analysis
Lipid Peroxidation
desmosome
metabolism
Acute-Phase Proteins
Zdroj: Journal of Physiology and Biochemistry
ISSN: 1877-8755
1138-7548
DOI: 10.1007/s13105-016-0545-x
Popis: Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1’s effects on liver by comparing wild-type controls, heterozygous igf1+/−, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage. Electronic supplementary material The online version of this article (doi:10.1007/s13105-016-0545-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE