© 1996 American Heart Association, Inc.
Articles |
Tenascin-C Is Induced With Progressive Pulmonary Vascular Disease in Rats and Is Functionally Related to Increased Smooth Muscle Cell Proliferation
the Division of Cardiovascular Research, Research Institute, The Hospital for Sick Children and Departments of Pediatrics, Pathology, and Medicine, University of Toronto (Canada).
Correspondence to Marlene Rabinovitch, MD, Division of Cardiovascular Research, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G 1X8. E-mail mr@sickkids.on.ca.
Tenascin-C, an extracellular matrix glycoprotein prominent during tissue remodeling, has been linked to cell migration, proliferation, and apoptosis. To determine its potential role in the pathobiology of pulmonary hypertension, we compared tenascin expression in adult and infant rat pulmonary arteries (PAs) after injection of the toxin monocrotaline. Immunohistochemistry, in situ hybridization, and Northern blot analysis demonstrated induction of tenascin in adult rat central and peripheral PA. Tenascin was not, however, detected in infant vessels, which show spontaneous regression of vascular lesions. To determine a function for tenascin, we correlated its expression with evidence of apoptosis and cell proliferation using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay and 5-bromo-2'-deoxyuridine labeling, respectively. Apoptosis was observed only in the adult rat PA endothelial cell layer, preceding the induction of tenascin, which colocalized both temporally and spatially with proliferating smooth muscle cells (SMCs). A cause-and-effect relationship was documented in cultured rat PA SMCs, where tenascin promoted growth in response to basic fibroblast growth factor and was a prerequisite for epidermal growth factor–induced proliferation. These data provide novel functional information suggesting that endothelial cell apoptosis precedes progressive pulmonary hypertension and that induction of tenascin may be critical to growth factor–dependent SMC proliferation.
Key Words: pulmonary hypertension • extracellular matrix • tenascin-C • cell proliferation • apoptosis
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