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Role of MMP‐2 activation in oncostatin‐M induced cardiomyocyte dedifferentiation
Author(s) -
Fan Frank Xiaohu,
Ali Mohammad A.M.,
Hughes Bryan G.,
Schulz Richard
Publication year - 2013
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.27.1_supplement.1146.4
Subject(s) - sarcomere , titin , microbiology and biotechnology , matrix metalloproteinase , myofibril , oncostatin m , troponin , chemistry , troponin complex , troponin i , myocyte , biology , medicine , biochemistry , inflammation , interleukin 6 , myocardial infarction
Despite the dogma that adult mammalian cardiomyocyte is terminally differentiated, these cells have a discrete regenerative capacity in both acutely and chronically injured human hearts. Dedifferentiation of cardiomyocytes is an important source of cardiac progenitor cells facilitating cardiac repair. Oncostatin‐M (OSM) can induce cardiomyocyte dedifferentiation characterized by sarcomere degeneration. However, the detailed mechanism regarding the downstream execution of sarcomere degeneration remains unclear. Matrix metalloproteinase‐2 (MMP‐2) is an important intracellular protease known to cleave multiple sarcomeric proteins including α‐actinin, troponin‐I and titin. We studied the dynamics of sarcomere degeneration upon stimulation of neonatal rat ventricular cardomyocytes (NRVM) with OSM. As early as 48 hr after OSM (50ng/ml) treatment, changes in sarcomeric structure were observed. Z‐bands stained for α‐actinin were degenerated towards Z‐bodies and M lines stained for titin also showed a similar pattern. The beating rate of NRVM significantly decreased, consistent with the observed sarcomere degeneration. Western blots and gelatin zymography analysis show increased MMP‐2 activity and loss of α‐actinin and troponin I following OSM treatment. These results suggest the possible involvement of MMP‐2 in cardiomyocyte dedifferentiation stimulated by OSM. Funding: Canadian Institutes of Health Research