title: Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.
abstract: BACKGROUND
  extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown.
  
  
  METHODS
  in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus).
  
  
  RESULTS
  following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis.
  
  
  CONCLUSIONS
  taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA.
authors.forename: Qia
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA ; Department of Medicine, University of California at San Francisco, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA ; Department of Medicine, University of California at San Francisco, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Lovett
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA.
authors.forename: Bryon
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Membrane Biology, University of California at Davis, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Bodine
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA ; Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.affiliation: San Francisco Veterans Affairs (VA), Medical Center, USA ; Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
keywords: basement membrane; extracellular matrix; matrix metalloproteinase-2; skeletal muscle hypertrophy; synergistic ablation