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 |
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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 |
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