Matrix metalloproteinase-2 regulates the expression of tissue inhibitor of matrix metalloproteinase-2.
1. Matrix metalloproteinases (MMP) are associated with the vascular remodelling seen in atherosclerosis and aneurysm. The activation and activity of MMP-2 are regulated by the intrinsic tissue inhibitor of MMP-2 (TIMP-2). The aim of the present study was to examine whether, conversely, MMP-2 can affect the gene and protein expression of TIMP-2. 2. In the present study, we examined the mRNA and protein expression of MMP-2 and TIMP-2 in cultured smooth muscle cells (SMC) from the aortas of MMP-2(+/+) and MMP-2(-/-) mice. We also examined the roles of MMP-2 in SMC cellular events. 3. Western blotting showed that less TIMP-2 protein was present in the conditioned medium of MMP-2(-/-) SMC than in that of MMP-2(+/+) SMC. Real-time reverse transcription polymerase chain reaction analysis showed that MMP-2 deficiency reduced TIMP-2 mRNA expression in SMC. Recombinant MMP-2 enhanced the expression of TIMP-2 protein in cultured SMC from MMP-2(-/-) mice. Furthermore, a siRNA targeting MMP-2 impaired the gene and protein expression of MMP-2 in cultured SMC from MMP-2(+/+) mice. MMP-2 deficiency impaired SMC invasion, but not their proliferation, adhesion or migration. 4. Our findings suggest that MMP-2 is likely to be responsible, at least in part, for regulating TIMP-2 expression and is thus a potential target, in addition to TIMP-2, for therapeutics aimed at preventing cardiovascular remodelling in response to injury.
Kimura
Kaoru
K
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Cheng
Xian Wu
XW
Nakamura
Kae
K
Inoue
Aiko
A
Hu
Lina
L
Song
Haizhen
H
Okumura
Kenji
K
Iguchi
Akihisa
A
Murohara
Toyoaki
T
Kuzuya
Masafumi
M
D000783:Aneurysm / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics
D034741:RNA, Small Interfering; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2