Essential roles of matrix metalloproteinases in axolotl digit regeneration

Among vertebrates, urodele amphibians possess a unique ability to regenerate various body parts including limbs. However, reports of their digit regeneration remain scarce, especially information about the related genes. In this study, it was evident that matrix metalloproteinases (mmps) including mmp9, mmp3/10a, and mmp3/10b, which play a crucial role in tissue remodeling, are highly expressed during early stages of digit regeneration in axolotl. Using in situ hybridization, we revealed that wound epidermis and blastema are two major origins of the MMPs during the regeneration process. Additionally, we found that the inhibition of MMPs with GM6001 (a wide-spectrum inhibitor of MMPs) in vivo after amputation disturbed normal digit regeneration process and resulted in malformed regenerates. Furthermore, inhibition of MMPs hindered blastema formation and decreased cell apoptosis at early stages in the digit regenerates. All these points suggest that MMPs are required for digit regeneration, as they play a significant role in the regulation of blastema formation.