Abstract
Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.
Highlights
The ectodysplasin A (EDA) gene is a member of the tumor necrosis factor (TNF) family located on the long arm of the X chromosome
Zhang et al (2009) found that Wnt/β-catenin signaling was necessary for the activation of the EDA/ectodysplasin A receptor (EDAR)/NF-κB signaling pathway in epithelial cells, as well as the subsequent morphological and molecular events required for hair follicle development
Nkx2-3 transfection inhibited cell proliferation and induced the expression of Bmp2 and Bmpr2 mRNA and the phosphorylation of Smad1/5/8 in dental epithelial stem cells (M3H1 cells). These results indicated that Nkx2-3 was induced by EDA-A1 as a target molecule of the EDA-A1/EDAR pathway in dental epithelial cells and subsequently regulated cell proliferation through the bone morphogenetic protein (BMP) signaling pathway
Summary
The ectodysplasin A (EDA) gene is a member of the tumor necrosis factor (TNF) family located on the long arm of the X chromosome. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, known as X-linked ectodermal dysplasia receptor (XEDAR). EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance.
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