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Interstitial flow induces vascular SMC migration in collagen I gels regulated by MMP‐1 via an ERK1/2‐dependent and c‐Jun‐mediated mechanism
Author(s) -
Shi ZhongDong,
Tarbell John M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.235.6
Subject(s) - matrix metalloproteinase , microbiology and biotechnology , chemistry , cell migration , neointima , gene silencing , extracellular matrix , vascular smooth muscle , c jun , mapk/erk pathway , cell , biology , signal transduction , medicine , biochemistry , endocrinology , smooth muscle , gene , restenosis , stent , transcription factor
Smooth muscle cells (SMC) migration into the intima after vascular injury is a central process in vascular lesion formation. The transmural interstitial flow is observed after damage to the vascular endothelium. In this study, the direct effects of interstitial flow on SMC migration were investigated in a 3‐dimensional collagen I gel system. Exposure of gels to a differential pressure of 1 cmH 2 O induced interstitial flow (shear stress ~0.05 dyn/cm 2 ) that substantially enhanced cell migration rate. Gene silencing suggested that flow‐induced migration was controlled by matrix metalloproteinase (MMP)‐1. PD‐98059, an ERK1/2 inhibitor, completely abolished flow‐induced migration and MMP‐1 expression. PD‐98059 also inhibited flow‐induced ERK1/2 activation and c‐Jun and c‐Fos expression. Silencing ERK1/2 or c‐jun completely abolished SMC migration and/or MMP‐1 expression, while knocking down c‐fos did not affect MMP‐1 expression. We also found that p38 MAPK and NF‐κB did not play major roles in flow‐induced MMP‐1 expression and cell migration. Taken together, our data indicate that interstitial flow induces MMP‐1 expression which in turn digests collagen matrix and promotes SMC migration via an ERK1/2‐dependent and c‐Jun‐mediated mechanism and suggest that interstitial flow may play an important role in SMC migration and neointima formation. Supported by NIH NHLBI grant RO1 HL 57093.