Midkine-a regulates the formation of a fibrotic scar during zebrafish heart regeneration

Midkine-a is a cytokine that is highly expressed in the heart upon injury that its role in regeneration has not been identified. We generated a KO zebrafish lines, mdkacn105, and studied the effect of mdka deletion in zebrafish adult heart regeneration. By combining histology and high-throughput genomics, we found that loss of mdka leads to arrest of heart regeneration. Mdka mutant hearts display increased collagen deposition in the site of the injury and decreased proliferation of the coronary endothelial cells due to increased expression of ECM including collagen and periostin as well as decreased expression of Hif1a. Our results demonstrate the importance of a balanced fibrotic respond is necessary for heart regeneration and indicates mdka importance in this process.