Functional MMP‐10 is required for efficient tissue repair after experimental hind limb ischemia
- 20 November 2014
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 29 (3), 960-972
- https://doi.org/10.1096/fj.14-259689
Abstract
We studied the role of matrix metalloproteinase-10 (MMP-10) during skeletal muscle repair after ischemia using a model of femoral artery excision in wild-type (WT) and MMP-10 deficient (Mmp10(-/-)) mice. Functional changes were analyzed by small animal positron emission tomography and tissue morphology by immunohistochemistry. Gene expression and protein analysis were used to study the molecular mechanisms governed by MMP-10 in hypoxia. Early after ischemia, MMP-10 deficiency resulted in delayed tissue reperfusion (10%, P < 0.01) and in increased necrosis (2-fold, P < 0.01), neutrophil (4-fold, P < 0.01), and macrophage (1.5-fold, P < 0.01) infiltration. These differences at early time points resulted in delayed myotube regeneration in Mmp10(-/-) soleus at later stages (regenerating myofibers: 30 ± 9% WT vs. 68 ± 10% Mmp10(-/-), P < 0.01). The injection of MMP-10 into Mmp10(-/-) mice rescued the observed phenotype. A molecular analysis revealed higher levels of Cxcl1 mRNA (10-fold, P < 0.05) and protein (30%) in the ischemic Mmp10(-/-) muscle resulting from a lack of transcriptional inhibition by MMP-10. This was further confirmed using siRNA against MMP-10 in vivo. Our results demonstrate an important role of MMP-10 for proper muscle repair after ischemia, and suggest that chemokine regulation such as Cxcl1 by MMP-10 is involved in muscle regeneration.Keywords
Funding Information
- Ministerio de Ciencia e Innovación (MICINN‐PTQ‐09‐02‐01941)
This publication has 40 references indexed in Scilit:
- A Call to Action: Women and Peripheral Artery DiseaseCirculation, 2012
- Matrix metalloproteinases and peripheral arterial diseaseInternal and Emergency Medicine, 2009
- Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuliFrontiers in Bioscience-Landmark, 2008
- Individual Matrix Metalloproteinases Control Distinct Transcriptional Responses in Airway Epithelial Cells Infected with Pseudomonas aeruginosaInfection and Immunity, 2007
- Regulation of Extracellular Matrix Remodeling following Transforming Growth Factor-β1/Epidermal Growth Factor-Stimulated Epithelial-Mesenchymal Transition in Human Premalignant KeratinocytesCells Tissues Organs, 2007
- Mechanisms Underlying the Impairment of Ischemia-Induced Neovascularization in Matrix Metalloproteinase 2–Deficient MiceCirculation Research, 2007
- MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung CarcinomasNeoplasia, 2004
- Experimental hindlimb ischemia leads to neutrophil-mediated increases in gastrocnemius MMP-2 and -9 activity: a potential mechanism for ischemia induced MMP activationJournal of Surgical Research, 2004
- Matrix Metalloproteinase-9 Is Required for Adequate Angiogenic Revascularization of Ischemic TissuesCirculation Research, 2004
- Increased expression of gelatinases and alteration of basement membrane in rat soleus muscle following femoral artery ligationNeuropathology and Applied Neurobiology, 2000