Alterations in tenascin synthesis, deposition and isoforms in lungs
from monocrotaline-induced pulmonary hypertensive rats.
Lipke, David L., Shewan M. Aziz, Jane A. Fagerland, Mark Majesky, and
Santosh S. Arcot.
Division of Pharmacology and Experimental Therapeutics, College of
Pharmacy, University of Kentucky, Lexington, KY 40536, Department of
Cellular and Microscopic Research, Abbott Laboratories, 45M/AP31, One
Abbott Park Road, Abbott Park, IL 60064, Department of Pathology,
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
4Human Genome Center, L-452, Lawrence Livermore National
Laboratories, Livermore, CA 94551
APStracts 3:0067L, 1996.
Monocrotaline (MCT)-induced pulmonary hypertension is characterized by
alterations in vascular extracellular matrix and neomuscularization
of small blood vessels. Tenascin (TN) is a matrix glycoprotein which
modulates cellular attachment, proliferation and migration. The
present study used immunohistochemistry and Northern analyses to
examine the hypothesis that treatment of rats with the potent
pneumotoxin MCT induces temporal alterations in TN
synthesis/deposition in the affected lungs. MCT produced progressive
pathological alterations in the cardiopulmonary system including
increased dry lung weight, right ventricular hypertrophy and
pulmonary hypertension by days 7, 14 and 21, respectively. TN
positive foci were first observed in the parenchyma surrounding small
muscularized pulmonary arteries in MCT treated rats at day 4; these
foci became both more pronounced and frequent as the disease
progressed. TN was also observed in the media of the intrapulmonary
artery at day 21. Northern analysis demonstrated increases in TN
transcripts in MCT-treated rats as early as day 1. Further, a unique
transcript, apparently lacking some fibronectin type III-like units
was observed in mRNA extracted from these rats. These data
demonstrate alterations in TN synthetic capacity and focal increases
in TN deposition in lungs from MCT-treated rats and suggest that TN
may be associated with the pathogenesis of pulmonary hypertension.
Received 3 October 1995; accepted in final form 28 March 1996.
APS Manuscript Number L292-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96