Induction of tenascin in rat lungs undergoing bleomycin-induced pulmonary fibrosis.
Lung injury induced by bleomycin is associated with early inflammation and subsequent excessive deposition of extracellular matrix. In the present study, we investigated the expression of extracellular matrix glycoprotein tenascin (TN) during pulmonary injury induced by bleomycin. After the initial lung injury induced by intratracheal bleomycin instillation, TN and collagen type III (COL III) mRNAs were greatly induced. The pattern of induction of TN was distinct from that of COL III. TN was primarily induced during the early inflammatory phase, whereas the increase in COL III synthesis continued during the reparative phase. The induction and localization of TN mRNA during bleomycin-induced pulmonary injury were also examined by in situ hybridization. TN mRNA was focally induced in rat lungs 3 days after bleomycin administration. Induction of TN mRNA was spatially restricted in the areas of tissue inflammation. The interstitial cells in alveolar septal walls and secondary septal tips in the areas of tissue damage were the major source of TN mRNA production. Expression of TN mRNA was decreased as the inflammation attenuated and development of fibrosis proceeded. Immunocytochemical analyses of TN protein distribution in the lung yielded corroborative results. Immunoreactive TN protein was found in a patchy distribution in alveolar septal walls and secondary septal tips in the areas of damaged tissues. This study demonstrated that TN is a unique early-response extracellular matrix component to bleomycin-induced pulmonary injury and is induced at the sites of the inflammation, suggesting a potential role of TN as a modulator of pulmonary inflammation and repair.
Zhao
Y
Y
Department of Medicine and of Pediatrics, Duke University Medical Center and Research Service, Durham Veterans Affairs Medical Center, Durham, North Carolina 27710, USA.
Young
S L
SL
McIntosh
J C
JC
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D003094:Collagen / Q000235:genetics; D015870:Gene Expression; D017403:In Situ Hybridization; D007700:Kinetics; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D019063:Tenascin; D001761:Bleomycin; D003094:Collagen