Altered hemodynamics controls matrix metalloproteinase activity and tenascin-C expression in neonatal pig lung.

Jones PL, Chapados R, Baldwin HS, Raff GW, Vitvitsky EV, Spray TL, Gaynor JW
Am J Physiol Lung Cell Mol Physiol. 2002 282 (1): L26-35

PMID: 11741812 · DOI:10.1152/ajplung.00171.2001

Tenascin-C (TN-C) expression and matrix metalloproteinase (MMP) activity are induced within remodeling pulmonary arteries (PAs), where they promote cell growth. Because pulmonary vascular disease in children with congenital heart defects is commonly associated with changes in pulmonary hemodynamics, we hypothesized that changes in pulmonary blood flow regulate TN-C and MMPs. To test this, we ligated the left PAs of neonatal pigs. After 12 wk, we evaluated the levels of TN-C and MMPs in control and ligated lung tissue. Modifying pulmonary hemodynamics increased TN-C mRNA and protein expression, MMP activity, and the DNA-binding activity of Egr-1, a transcription factor that has been shown to activate TN-C expression. To link MMP-mediated remodeling of the extracellular matrix to increased TN-C expression and Egr-1 activity, porcine PA smooth muscle cells were cultivated either on denatured type I collagen, which supported TN-C expression and Egr-1 activity, or on native collagen, which had the opposite effect. These data provide a framework for understanding how changes in pulmonary blood flow in the neonate modify the tissue microenvironment and cell behavior.

MeSH Terms (20)

Animals Animals, Newborn Cells, Cultured Collagen DNA DNA-Binding Proteins Enzyme Activation Female Hemodynamics Lung Male Matrix Metalloproteinases Muscle, Smooth, Vascular Pulmonary Artery Pulmonary Circulation RNA, Messenger Swine Tenascin Transcription Factors Up-Regulation

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