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

Abstract

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 materialThe online version of this article (doi:10.1007/s13105-016-0545-x) contains supplementary material, which is available to authorized users.

Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profiles of human joint fibroblast‐like synoviocytes

“…53 Besides, Lara-Diza et al have uncovered that the IGF1 could regulate the expression of the IGF1 receptor and acute-phase inflammation mediators, which aggravate cell damage through oxidative stress pathway. 54 SELE has been demonstrated the function of assembling leukocytes at inflammatory sites through promoting the adhesion of cells. 55 Some studies have also reported that SELE-mediated adhesion of leukocytes or tumour cells to the vascular endothelium was an important progress in the initiation of inflammatory response and metastasis of cancer cells.…”

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins

“…Although these findings are difficult to explain, some facts shed light over them. First of all, previous work using this same experimental model found that the single partial IGF-1 deficiency was associated with an altered structure of several organs, such as the brain [ 26 ], liver [ 25 ], and testicle [ 30 ]. Furthermore, the present study shows that hearts belonging to non-treated IGF-1-deficient mice overexpress Serpine1 and Serpinh1 , being sensitive to IGF-1 replacement therapy ( Fig 7 ).…”

“…As previously reported [ 1 , 25 , 26 ], heart mRNA was isolated from animals belonging to the three experimental groups in accordance with the protocol outlined in RNAqueousH-Micro Kit (Ambion, USA). Technical procedures for microarray analysis, including quality control of mRNA, labeling, hybridization and scanning of the arrays were performed according to standard operating procedures for Affymetrix protocols (GeneChipH Expression Analysis Manual, Affymetrix, USA).…”

Is insulin-like growth factor-1 involved in Parkinson’s disease development?

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