| Summary: | <i>c-Fos</i> is an immediate-early gene that modulates cellular responses to a wide variety of stimuli and also plays an important role in tissue regeneration. However, the sequence and functions of <i>c-Fos</i> are still poorly understood in newts. This study describes the molecular cloning and characterization of the <i>c-Fos</i> gene (<i>Co-c-Fos</i>) of the Chinese fire-bellied newt, <i>Cynops orientalis</i>. The full-length <i>Co-c-Fos</i> cDNA sequence consists of a 1290 bp coding sequence that encoded 429 amino acids. The alignment and phylogenetic analyses reveal that the amino acid sequence of <i>Co-c-Fos</i> shared a conserved basic leucine zipper domain, including a nuclear localization sequence and a leucine heptad repeat. The <i>Co-c-Fos</i> mRNA is widely expressed in various tissues and is highly and uniformly expressed along the newt limb. After limb amputation, the expression of <i>Co-c-Fos</i> mRNA was immediately upregulated, but rapidly declined. However, the significant upregulation of Co-c-Fos protein expression was sustained for 24 h, overlapping with the wound healing stage of <i>C. orientalis</i> limb regeneration. To investigate if <i>Co-c-Fos</i> participate in newt wound healing, a skin wound healing model is employed. The results show that the treatment of T-5224, a selective c-Fos inhibitor, could largely impair the healing process of newt’s skin wound, as well as the injury-induced <i>matrix metalloproteinase-3</i> upregulation, which is fundamental to wound epithelium formation. These data suggest that <i>Co-c-Fos</i> might participate in wound healing by modulating the expression of its potential target gene <i>matrix metalloproteinase-3</i>. Our study provides important insights into mechanisms that are responsible for the initiation of newt limb regeneration.
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