Nuclear MMP-9 role in the regulation of rat skeletal myoblasts proliferation

Abstract

Background information: Matrix metalloproteinases (MMPs) are the key enzymes responsible for the remodelling of extracellular matrix. Two of them, namely MMP-2 and MMP-9 (gelatinases A and B, respectively), are expressed in skeletal muscles and are involved in their regeneration after the injury. Although MMPs are primarily known to act extracellularly, recent studies have shown that some of them are also found within the cell. In this study, we examine intracellular localisation of gelatinases during myoblasts differentiation in vitro, focussing the impact of MMPs inhibition on the myoblasts proliferation and function.

Results: We show that MMP-9 localises within the S-phase nuclei of in vitro differentiating myoblasts. The inhibition of MMPs activity achieved by either doxycycline (a non-competitive inhibitor of collagenases), TIMP-1 (tissue inhibitor of metalloproteinases 1) or neutralising anti-MMP-9 antibody affects nuclear localisation of this gelatinase, and impacts at myoblasts proliferation.

Conclusions: During myoblasts differentiation, MMP-9 that is localised in nuclei might be involved in the processes regulating cell cycle progression.

Keywords: Differentiation; MMP-9; Myoblast; Nucleus; Proliferation.