Background:Transforming growth factor (TGF)-␤ signaling depends on decorin and LRP-1. Results: Decorin internal regions 5 and 6 interact with LRP-1 to modulate TGF-␤ mediated signaling. Conclusion: A specific decorin region regulates TGF-␤-dependent signaling. Significance: Identification of specific sites in decorin that are involved in TGF-␤ signaling might have potential therapeutic applications for treatment of fibrotic diseases.

Varying levels of lupin (Lupinus albus), peas (Pisum sativum) and rapeseed (Brassica napus) meals were evaluated as partial replacements for fishmeal in extruded diets for rainbow trout, with particular emphasis on the effect on growth performance and the expression of three genes associated with immune response. A series of 10 isonitrogenous (450 g kg À1 crude protein) and isolipidic (17 g kg À1 crude lipid) diets were formulated to contain different levels of lupin (150 g kg À1 , 250 g kg À1 and 350 g kg À1 ), rapeseed cake (100 g kg À1 , 200 g kg À1 and 300 g kg À1 ) and pea (50 g kg À1 , 150 g kg À1 and 250 g kg À1 ) meals. The control diet was prepared with fish meal as the sole source of protein. Triplicate groups of fish (37.08 ± 3.58 g) were assigned to each experimental diet. The feeding experiment was conducted for 9 weeks at 14.3 ± 0.4°C. The fish were hand fed three times per day, 6 days per week to apparent satiation level. Growth performance, feed utilization and immunological response were significantly affected by the type of plant protein as well as level of inclusion. Hepatosomatic index (HSI) increased in all groups of fish fed diets with pea and rapeseed cake meal. Dietary inclusion of lupin did not affect the expression of Mx-1 gene. Our results suggest that fish meal can be replaced by lupin in the diet of rainbow trout without any apparent adverse effects on key innate immunological genes.

Fibrotic disorders are characterized by an increase in extracellular matrix protein expression and deposition, Duchene Muscular Dystrophy being one of them. Among the factors that induce fibrosis are Transforming Growth Factor type β (TGF-β) and the matricellular protein Connective Tissue Growth Factor (CTGF/CCN2), the latter being a target of the TGF-β/SMAD signaling pathway and is the responsible for the profibrotic effects of TGF-β. Both CTGF and TGF are increased in tissues affected by fibrosis but little is known about the regulation of the expression of CTGF mediated by TGF-β in muscle cells. By using luciferase reporter assays, site directed mutagenesis and specific inhibitors in C2C12 cells; we described a novel SMAD Binding Element (SBE) located in the 5' UTR region of the CTGF gene important for the TGF-β-mediated expression of CTGF in myoblasts. In addition, our results suggest that additional transcription factor binding sites (TFBS) present in the 5' UTR of the CTGF gene are important for this expression and that SP1/SP3 factors are involved in TGF-β-mediated CTGF expression.

Infectious pancreatic necrosis virus (IPNV) is an economically important pathogen of the salmonid aquaculture industry. Selective breeding has been employed to improve resistance to this infectious disease, and it is of importance to investigate the expression profile of immune genes of Atlantic salmon with different genetic background in response to this virus. This study examined the immune modulation response of eight candidate genes in head kidney tissue in two families of Atlantic salmon with high and low mortalities, after challenge with IPNV. The results showed that the expression pattern of target genes differed in the two families. Generally, higher expression of antiviral, pro-inflammatory genes and transcription factors such as tripartite motif, NF-κB, IFNI, STAT1, protein kinase R, and Vig-2 in the resistant family were observed at the same time point. One may speculate the functional importance of these putative candidate genes in the characterization of the IPNV-resistant (low mortalities) immune phenotype. Therefore, on our findings, we suggest that future salmonids studies aiming to identify candidate genes/pathway or vaccines evaluation should consider validating detected genes/pathway across different genetic backgrounds or immune phenotype.

Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model.