Tenascin synthesis, deposition, and isoforms in monocrotaline-induced pulmonary hypertensive rat lungs.
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. Furthermore, 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.
Lipke
D L
DL
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536, USA.
Aziz
S M
SM
Fagerland
J A
JA
Majesky
M
M
Arcot
S S
SS
D000818:Animals; D015152:Blotting, Northern; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007536:Isomerism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D011042:Poisons / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D011042:Poisons; D012333:RNA, Messenger; D019063:Tenascin; D016686:Monocrotaline