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Matrix Metalloproteinase Changes in a Cachectic Mouse Model
Author(s) -
Devine Raymond,
Bicer Sabahattin,
Reiser Peter,
Wold Loren
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1045.7
Subject(s) - cachexia , matrix metalloproteinase , myocyte , skeletal muscle , extracellular matrix , cancer , cardiac muscle , biology , medicine , cancer research , endocrinology , pathology , microbiology and biotechnology
Cardiac and skeletal muscle dysfunction is a recognized effect of cancer‐induced cachexia. Cachexia is associated with changes in the heart, leading to clinical presentation of heart failure. In skeletal muscle, there is a decrease in myofiber diameter along with an inability to form new myoblasts. The ubiquitin system, responsible for marking proteins for degradation, has been implicated in the progression of cancer cachexia. Cachexia is a complex and multifaceted disease state with several potential contributors to the pathology. Matrix metalloproteinases (MMPS) are a family of enzymes capable of degrading components of the extracellular matrix (ECM) that may play a role in pathology common to cachexia. Changes to the ECM cause disruption in the connections between cells, at the basement membrane, and cell‐to‐cell interactions. In the present study, we used a murine model of cancer cachexia to determine if there are changes in gene expression of MMPs in striated muscle (Fig 1)and protein expression in striated muscle (Fig 2.)Because of the large number of MMPs, we narrowed down our analysis to MMP‐2, ‐3, ‐9, and ‐14. These represent the MMPs that have been shown to contribute to both cardiac and skeletal muscle ECM changes. Our findings demonstrate a significant, increase in MMP protein and mRNA expression in cardiac and skeletal muscle. With these findings, MMPs represent a possible therapeutic avenue to treat cachexia associated with cancer.