A major goal of regenerative medicine is to develop therapies that can improve the recovery of heart muscle cells after a heart attack and restore normal heart activity to patients with heart failure.
Unlike the human heart, the heart of an adult zebrafish is able to regenerate even after extensive damage. After an injury, the remaining heart muscle cells divide to replace the lost heart muscle, but it is not clear how this works.
In a study published April 1, published in the online open-access journal eLife, researchers Matthew Gemberling, Ravi Karra, Amy L Dickson and Kenneth D Poss investigate this process in the zebrafish and look at whether – and how – any of it can be applied to humans.
They focused on a protein called Neuregulin1 (Nrg1) that can stimulate heart muscle cells to divide. Their experiments show that when the heart is injured, the gene encoding the Nrg1 protein is switched on in cells of the outer layer of the heart wall. When Nrg1 is deliberately activated in uninjured adult zebrafish hearts, it causes the muscle cells to divide, leading to many new layers of heart muscle forming over the course of several weeks. Along with promoting cell division, Nrg1 also makes the heart muscle cells return to an immature state more like stem cells. Gemberling et al.’s findings demonstrate that Nrg1 is sufficient to induce the growth of heart muscle growth in an adult animal, even in the absence of injury. To develop its therapeutic potential, future work will also need to identify how the gene that encodes Nrg1 is switched on by injury and identify the other molecules that interact with Nrg1.
The next generation of genome editing-inspired tools for zebrafish researchers should enable tests of cell-restricted, inducible genetic deletion of key Nrg1 components in multiple cell types. These experiments promise to dissect and define Nrg1 signaling requirements for regenerative responses within the complex cardiac milieu.
It will be critical to define the mechanisms by which Nrg1 is induced by injury in zebrafish and restricted in the absence of trauma, as well as downstream Nrg1 targets in the regeneration program. Such investigation of the endogenous regulation of Nrg1 after cardiac injury can help guide methodology to optimize its delivery and impact on heart regeneration in mammals.
Read the Full Study here: http://lens.elifesciences.org/05871/index.html?_ga=1.105521472.2107951736.1427907857#content/contributor_reference_2
