MicroRNA-29b inhibits migration and proliferation of vascular smooth muscle cells in neointimal formation.
The proliferation and migration of smooth muscle cells (SMCs) are considered to be key steps in the progression of atherosclerosis and restenosis. Certain stimuli, such as, interleukin-3 (IL-3) are known to stimulate proliferation and migration in vascular diseases. Meanwhile, microRNAs (miRs) have been revealed as critical modulators of various diseases in which miR-29b is known to regulate cell growth by targeting Mcl-1 and MMP2. However, roles of miR-29b in vascular smooth muscle cells remain almost unknown. We hypothesized that miR-29b may control the proliferation and migration processes induced by IL-3 stimulation by inhibiting its own specific targets in SMCs. MiR-29b significantly suppressed the proliferation and migration of SMCs through the inhibition of the signaling pathway related to Mcl-1 and MMP2. We also found that miR-29b expression levels significantly declined in balloon-injured rat carotid arteries and that the overexpression of miR-29b by local oligonucleotide delivery can inhibit neointimal formation. Consistent with the critical role of miR-29b in vitro, we observed down-regulated expression levels of Mcl-1 and MMP2 from the neointimal region. These results indicate that miR-29b suppressed the proliferation and migration of SMCs, possibly through the inhibition of Mcl-1 and MMP2, and suggest that miR-29b may serve as a useful therapeutic tool to treat cardiovascular diseases such as, atherosclerosis and restenosis.
Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
Jiyun
J
Lee
Soyeon
S
Lim
Byeong-Wook
BW
Song
Min-Ji
MJ
Cha
Onju
O
Ham
Se-Yeon
SY
Lee
Changyoun
C
Lee
Jun-Hee
JH
Park
Yoonjin
Y
Bae
Hyang-Hee
HH
Seo
Minji
M
Seung
Eunhyun
E
Choi
Ki-Chul
KC
Hwang
D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007377:Interleukin-3 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D058426:Neointima / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007377:Interleukin-3; C526366:MIRN29 microRNA, rat; C579093:Mcl1 protein, rat; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat
MIGRATION; MicroRNA-29b; PROLIFERATION; SMOOTH MUSCLE CELL