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Matrix metalloproteinase‐2 mediate oncostatin‐M induced cardiomyocyte dedifferentiation (1151.2)
Author(s) -
Fan Frank,
Ali Mohammad,
Hughes Bryan,
Launier Katherine,
Schulz Richard
Publication year - 2014
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.28.1_supplement.1151.2
Subject(s) - sarcomere , microbiology and biotechnology , matrix metalloproteinase , myofibril , myocyte , extracellular matrix , chemistry , biology , biochemistry
Dedifferentiated cardiomyocytes are an important source of cardiac progenitor cells facilitating cardiac repair. Cardiomyocyte dedifferentiation induced by oncostatin‐M (OSM) is characterized by progressive sarcomere degeneration. However, the mechanism regarding the execution of sarcomere degeneration remains unclear. Matrix metalloproteinase‐2 (MMP‐2) is a key intracellular protease abundantly expressed in cardiomyocytes. We hypothesized that MMP‐2 may be involved in cardiomyocyte dedifferentiation. We performed confocal immunofluorescence and biochemical studies to explore the role of MMP‐2 in OSM‐induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). Cells treated with OSM (10‐200 ng/ml for 1‐5 days) showed a dose and time‐dependent loss of sarcomeric α‐actinin and troponin‐I. The mature sarcomere transformed to a pattern resembling a less developed sarcomere (Z‐disks transformed into Z‐bodies usually found in immature myofibrils). Western blots and gelatin zymography showed that OSM treatment dose‐dependently increased MMP‐2 activity. Both selective MMP‐2 inhibitor (ARP100, 100 µM) and pan‐MMP inhibitors (GM6001, 5 µM) rescued OSM‐induced sarcomere degeneration. These results suggest that intracellular MMP‐2 mediates sarcomere degeneration in OSM‐induced cardiomyocyte dedifferentiation and potentially contributes to cardiomyocyte regeneration. Grant Funding Source : The Canadian Institutes of Health Research (CIHR)