Post-translational activation of mmp2 by mmp14 is triggered by mechanical signalling through Piezo1 and Erk during embryonic growth in zebrafish

Abstract

To grow and change shape during development, wound healing and regeneration, multicellular tissues must remodel their extracellular matrix (ECM). The matrix metalloproteinases (MMPs) are the primary effectors of ECM remodeling. Using a transgenic zebrafish, we can visualize the activation of Mmp2 in intact embryos. Piezo1 is a stretch-sensitive, cation channel that is abundant in the epidermis of zebrafish embryos; I hypothesized that activation of Piezo1 triggers expression of Mmp14 via Erk signalling, resulting in Mmp2 activation. Consistent with this hypothesis, I observed increased mmp14b expression after treatment with the Piezo1 agonist Yoda1, and decreased mmp14b expression after treatment with either the Piezo1 inhibitor GsMTx4 or the MEK/ERK inhibitor PD0325901. I also found increased Mmp2 activation following treatment with Yoda1, and reduction of Mmp2 activation following treatment with GsMTx4 or PD0325901. These findings suggest a new link between stretching of epithelial tissues and the biochemical mechanisms of ECM remodeling in vivo.