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

• Published in: Molecular and cellular biochemistry Vol. 368; no. 1-2; pp. 27 - 35
• Main Authors: Dey, Nupur B., Lincoln, Thomas M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-09-2012; Springer; Springer Nature B.V
• Subjects: Animals; Aorta - cytology; Aorta - enzymology; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Movement - physiology; Cell Proliferation; Cellular biology; Cyclic GMP - metabolism; Cyclic GMP-Dependent Protein Kinases - metabolism; Gene Expression Regulation, Enzymologic - physiology; Kinases; Life Sciences; Male; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Medical Biochemistry; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - enzymology; Nitric oxide; Nitric Oxide Synthase Type III - biosynthesis; Nitric Oxide Synthase Type III - blood; Oncology; Peptides; Protein kinases; Proteins; Rats; Rats, Sprague-Dawley; RNA; Rodents; Smooth muscle; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; Matrix metalloproteinases-2; Transfection; DT-2; PKG; Vascular smooth muscle cells
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1339-2

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.