Journal article
P. Mishra, Naira S. Metreveli, Vishalakshi Chavali, N. Tyagi, Natia Qipshidze, U. Sen, I. Joshua, S. Tyagi
2012
2012
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APA
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Mishra, P., Metreveli, N. S., Chavali, V., Tyagi, N., Qipshidze, N., Sen, U., … Tyagi, S. (2012). Role Of MMP9 In Cardiac Stem Cell Differentiation And Autophagy.
Chicago/Turabian
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Mishra, P., Naira S. Metreveli, Vishalakshi Chavali, N. Tyagi, Natia Qipshidze, U. Sen, I. Joshua, and S. Tyagi. “Role Of MMP9 In Cardiac Stem Cell Differentiation And Autophagy” (2012).
MLA
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Mishra, P., et al. Role Of MMP9 In Cardiac Stem Cell Differentiation And Autophagy. 2012.
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@article{p2012a,
title = {Role Of MMP9 In Cardiac Stem Cell Differentiation And Autophagy},
year = {2012},
author = {Mishra, P. and Metreveli, Naira S. and Chavali, Vishalakshi and Tyagi, N. and Qipshidze, Natia and Sen, U. and Joshua, I. and Tyagi, S.}
}
Abstract
To test the hypothesis that ablation of MMP9 induces cardiac stem cell (CSC) differentiation into cardiomyocytes and inhibits autophagy, we created double knock out (DKO: Ins2+/−/MMP9−/−) mice. The levels of CSC, cardiomyomyocytes and autophagy were determined in the heart of C57BL/6J (WT), Ins2+/− (diabetic) and DKO mice by RT‐PCR, immunocytochemistry, confocal microscopy and Western blotting using c‐kit, troponin and LC3 markers, respectively. The ECM turn over (fibrosis) was measured by Masson Trichrome staining. The cross talk between c‐kit and MMP9 was determined by co‐immunoprecipitation (co‐IP). Interestingly, the degree of fibrosis was correlated with the levels of LC3 and troponin in the WT, Ins2+/− and DKO (mean ± SE: fibrosis −14± 2.1, 34±2.5, 6±1.9; LC3−36±1.5; 39± 0.6, 38±1.0; and troponin−11.2± 0.4, 8.8±0.3, 12.3± 0.28, respectively). Western blot and co‐IP results revealed that induction of MMP9 attenuates c‐kit in the diabetic heart. Based on these findings, it is suggested that robust expression of MMP9 exacerbates autophagy and alleviates cardiomyocytes in diabetes. Our results elicit a novel mechanism, where abrogation of MMP9 promotes differentiation of CSC into cardiomyocytes and improves their survival by inhibiting autophagy.