Regulation of Embryonic Wound Healing by Matrix Metalloproteinases in Xenopus laevis Tailbud Stage

Scarless wound healing remains a key goal in regenerative research. However, the gene regulatory networks and mechanisms behind this process are still not fully understood, despite the use of high-throughput analyses and various research models. In our study, we focus on the intermediate phase and examine the role of remodelling genes called matrix metalloproteinases (MMPs) in the Xenopus laevis model. Through temporal bulk RNA-Seq analysis, we identified the fos/jun (AP-1) combination expressed during the early phase and four main mmps (1, 7, 8, and 9) expressed during the intermediate phase of healing. Using specific MMP inhibitors and morpholino-oligonucleotides targeting fos/jun, we found that mmp expression depends on stress response and that they are crucial for embryonic wound healing. We also analysed other published healing data sets (single cell and bulk RNA-Seq) and observed a strong correlation of our observations with healing in mammals. In summary, our study indicates that wound healing is a conserved biological process that begins with a stress response involving AP-1. It then progresses through the stage of extensive healing activity, including the expression induction of specific mmp genes during the remodelling phase.