title: 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.
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: V J
authors.initials: VJ
authors.lastname: Lara-Diaz
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico. iccortazar@itesm.mx.|Fundacion de Investigacion HM Hospitales, Madrid, Spain. iccortazar@itesm.mx.
authors.forename: I
authors.initials: I
authors.lastname: Castilla-Cortazar
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Martín-Estal
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: García-Magariño
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: G A
authors.initials: GA
authors.lastname: Aguirre
authors.affiliation: Department of Medical Physiology, School of Medicine, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: J E
authors.initials: JE
authors.lastname: Puche
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: R G
authors.initials: RG
authors.lastname: de la Garza
authors.affiliation: Escuela de Medicina, Tecnologico de Monterrey, Avenida Morones Prieto No. 3000 Pte. Col. Los Doctores, 64710, Monterrey, Nuevo León, Mexico.
authors.forename: L A
authors.initials: LA
authors.lastname: Morales
authors.affiliation: Department of Medical Physiology, School of Medicine, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: U
authors.initials: U
authors.lastname: Muñoz
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism*; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D017451:Receptors, Somatomedin; D062725:Tight Junction Proteins; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I
keywords: Cytoskeleton; Extracellular matrix; Gene expression; Hepatocytes; IGF-1; Tight junctions