Gpnmb is required for immune and fibrotic responses during zebrafish heart regeneration

In contrast to adult humans, adult zebrafish have a unique ability to regenerate their heart after cardiac injury. To identify potential regulators of the regenerative response, we performed transcriptomic profiling of regenerating coronary endothelial cells (cECs) at 7 days post cryoinjury, when revascularization is vigorous, and identified gpnmb to be upregulated.

Gpnmb (glycoprotein non-metastatic melanoma protein B) is a transmembrane glycoprotein implicated in inflammation resolution and tissue regeneration. Expression analyses at earlier time points revealed gpnmb specific expression in infiltrating macrophages post cryoinjury in zebrafish ventricles. Using newly generated gpnmb mutants, we analyze its role during heart regeneration and find that animals lacking gpnmb exhibit neutrophil retention and decreased macrophage recruitment as well as reduced myofibroblasts numbers.