-This review presents a broad overview of chorionic glycoproteins encoded by the Pregnancy-Associated Glycoprotein (PAG) gene family and also serves to illustrate how the recent discovery of the PAG family has contributed to our general knowledge of genome evolution, placental transcription and placental protein expression. The complex and large PAG family is restricted to the Artiodactyla order, although single PAG-like genes have also been identified in species outside the Artiodactyla. The PAGs are members of the aspartic proteinase (AP) superfamily. Unexpectedly, however, some members of the PAG family possess amino acid substitutions within and around the active site that likely render them unable to act as proteinases. This paper summarises the available information regarding biodiversity of PAG gene expression based on cDNA cloning, mRNA localisation studies and the structural organisation of the PAG genes with a particular emphasis on PAG promoters. It also compares available data regarding PAG protein purifications, sequencing and their N-glycodiversity. Finally, it discusses the scientific relevance, possible functional roles of the PAGs and describes possible profitable applications related to the detection of PAG proteins in the blood of pregnant domestic and wild species. chorionic glycoproteins / eutherian PAG family / diagnostic PAG markers
FOXN1, a transcription factor expressed in the epidermis, regulates keratinocyte differentiation and participates in skin wound healing. In this study, we explored the impact of FOXN1 insufficiency on diet-stimulated weight gain and dermal white adipose tissue regulation in the intact and wounded skin of FOXN1 eGFP/þ (heterozygotes, FOXN1-insufficient) mice in the context of age and diet. The results showed that on a high-fat diet, FOXN1 eGFP/þ mice gained significantly less body weight than their FOXN1 þ/þ counterparts (FOXN1-sufficient mice). The intact and wounded skin of FOXN1 eGFP/þ mice displayed abrogated expression of the master regulators of adipogenesis, PPARg, FABP4, and leptin, which decreased with age in FOXN1 þ/þ mice. FOXN1 insufficiency also resulted in a decreased percentage of adipocyte-committed precursor cells (CD24 þ) in the skin. The proadipogenic pathway genes Bmp2, Igf2, and Mest showed a gradual decrease in expression that accompanied the gradual inactivation of FOXN1 in the skin of FOXN1 þ/þ , FOXN1 eGFP/þ , and FOXN1 eGFP/eGFP (lack of FOXN1) mice. Bone morphogenetic protein 2 and insulin-like growth factor 2 signals colocalized with FOXN1-eGFP in the epidermis and in hair follicles. These data demonstrated that FOXN1 initiates the cascade of adipogenic signaling that regulates skin homeostasis and wound healing and affects susceptibility to dietinduced obesity.
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