Mechanisms of Collagen Network Organization in Response to Tissue/Organ Damage

Fibrosis is a part of the wound-healing response to tissue damage and characterized by excessive accumulation of mainly type I collagen-containing extracellular matrices (ECMs). Transforming growth factor beta (TGF-β) is a profibrogenic master cytokine responsible for promoting differentiation of tissue-resident fibroblasts into myofibroblasts, upregulation of ECM production, and downregulation of ECM degradation. The formation of ECM is an essential response in wound healing. Fibronectin is an ECM glycoprotein substantially expressed during tissue repair. Based on in vitro findings, it has been widely accepted that collagen network organization was exclusively fibronectin matrix dependent. Unexpectedly, our fibronectin conditional knockout mouse models have demonstrated a fibronectin-independent mechanism of collagen fibril formation following injury and identified TGF-β signaling and type V collagen as essential elements for collagen fibrillogenesis. Interestingly, the targeting of the TGF-β signaling alone, as proposed in some recent antifibrotic therapies of chronic fibrotic diseases, is not sufficient to completely prevent liver fibrosis. In this chapter, we focus on the present knowledge of the mechanisms of the collagen network organization following tissue/organ damage and pathological processes of chronic fibrotic diseases

Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM) influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis

Regulation of Agouti-Related Protein and Pro-Opiomelanocortin Gene Expression in the Avian Arcuate Nucleus

The arcuate nucleus is generally conserved across vertebrate taxa in its neuroanatomy and neuropeptide expression. Gene expression of agouti-related protein (AGRP), neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) has been established in the arcuate nucleus of several bird species and co-localization demonstrated for AGRP and NPY. The proteins encoded by these genes exert comparable effects on food intake in birds after central administration to those seen in other vertebrates, with AGRP and NPY being orexigenic and CART and α-melanocyte-stimulating hormone anorexigenic. We have focused on the measurement of arcuate nucleus AGRP and POMC expression in several avian models in relation to the regulation of energy balance, incubation, stress, and growth. AGRP mRNA and POMC mRNA are, respectively, up- and downregulated after energy deprivation and restriction. This suggests that coordinated changes in the activity of AGRP and POMC neurons help to drive the homeostatic response to replace depleted energy stores in birds as in other vertebrates. While AGRP and POMC expression are generally positively and negatively correlated with food intake, respectively, we review here situations in some avian models in which AGRP gene expression is dissociated from the level of food intake and may have an influence on growth independent of changes in appetite. This suggests the possibility that the central melanocortin system exerts more pleiotropic functions in birds. While the neuroanatomical arrangement of AGRP and POMC neurons and the sensitivity of their activity to nutritional state appear generally conserved with other vertebrates, detailed knowledge is lacking of the key nutritional feedback signals acting on the avian arcuate nucleus and there appear to be significant differences between birds and mammals. In particular, recently identified avian leptin genes show differences between bird species in their tissue expression patterns and appear less closely linked in their expression to nutritional state. It is presently uncertain how the regulation of the central melanocortin system in birds is brought about in the situation of the apparently reduced importance of leptin and ghrelin compared to mammals

Myostatin Increases Smad2 Phosphorylation and Atrogin-1 Expression in Chick Embryonic Myotubes

Skeletal muscle mass is an important trait in poultry meat production. In mammals, myostatin, a negative regulator of skeletal muscle growth, activates Smad transcription factors and induces the expression of atrogin-1 by regulating the Akt/FOXO pathway. Although the amino acid sequence of chicken myostatin is known to be completely identical to its mammalian counterpart, previous studies in chicken skeletal muscles have implied that the physiological roles of chicken myostatin are different from those of mammals. Furthermore, it remains to be elucidated whether myostatin affects cellular signaling factors and atrogin-1 expression. In this study, using chick embryonic myotubes, we found that myostatin significantly increased the phosphorylation rate of Smad2 and mRNA levels of atrogin-1. No significant change was observed in the phosphorylation of Akt and FOXO1. These in vitro results suggest that the molecular mechanisms underlying myostatin-induced expression of atrogin-1 might be different between chickens and mammals

Gut Hormones and Regulation of Food Intake in Birds

Gut hormones act as appetite regulatory hormones in mammals. For example, the hunger hormone ghrelin, which is released from the stomach before food intake, stimulates appetite. In contrast, satiety hormones such as cholecystokinin, glucagon-like peptide-1, and peptide YY, which are released from the intestines after food intake, suppress appetite. The effects of these peptides on food intake have been shown to be similar in both mammals and fishes. However, evidence suggests that the physiological roles of these gut hormones may be different between birds and other vertebrates. This review summarizes the current information on the roles of gut hormones in the regulation of food intake in birds, especially in chickens