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Possible involvement of Cyclic-GMP-dependent protein kinase on matrix metalloproteinase-2 expression in rat aortic smooth muscle cells

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Abstract

Degradation and resynthesis of the extracellular matrix (ECM) are essential during tissue remodeling. Expansion of the vascular intima in atherosclerosis and restenosis following injury is dependent upon smooth muscle cell (SMC) proliferation and migration. The migration of SMC from media to intima critically depends on degradation of ECM protein by matrix metalloproteinases (MMPs). MMP inhibitors and eNOS gene transfer have been shown to inhibit SMC migration in vitro and neointima formation in vivo. Nitric oxide (NO) and cyclic-GMP have been implicated in the inhibition of VSMC migration. But, there are few studies addressing the role of NO signaling pathways on the expression of MMPs. Here we reported the involvement of cyclic-GMP-dependent protein kinase (PKG) (an important mediator of NO and cGMP signaling pathway in VSMC) on MMP-2 expression in rat aortic SMC. The goal of the present study was to gain insight into the possible involvement of PKG on MMP-2 in rat aortic SMC. MMP-2 protein and mRNA level and activity were downregulated in PKG-expressing cells as compared to PKG-deficient cells. In addition, the secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased in PKG-expressing cells as compared to PKG-deficient cells. PKG-specific membrane permeable peptide inhibitor (DT-2) reverses the process. Interestingly, little or no changes of MMP-9 were observed throughout the study. Taken together our data suggest the possible role of PKG in the suppression of MMP-2.

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Acknowledgments

This work was supported by a grant from the NIH (HL66164).

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  1. Department of Physiology, College of Medicine, University of South Alabama, Mobile, AL, 36688, USA

    Nupur B. Dey & Thomas M. Lincoln

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  1. Nupur B. Dey
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  2. Thomas M. Lincoln
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Correspondence to Nupur B. Dey.

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Dey, N.B., Lincoln, T.M. Possible involvement of Cyclic-GMP-dependent protein kinase on matrix metalloproteinase-2 expression in rat aortic smooth muscle cells. Mol Cell Biochem 368, 27–35 (2012). https://doi.org/10.1007/s11010-012-1339-2

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  • DOI: https://doi.org/10.1007/s11010-012-1339-2

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