Expression of transforming growth factor-β type I and type II receptors is altered in rat lungs undergoing bleomycin-induced pulmonary fibrosis

被引:25
作者
Zhao, Y
Shah, DU
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Durham Vet Affairs Med Ctr, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
TGF-beta; TGF-beta type I receptor; TGF-beta type II; receptor; pulmonary fibrosis; lung injury; extracellular matrix; bleomycin;
D O I
10.1006/exmp.2000.2319
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Transforming growth factor-beta (TGF-beta) is a family of autocrine/ paracrine/endocrine cytokines involved in controlling cell growth and extracellular matrix metabolism. TGF-beta exerts its biological effects via binding to type I (T beta RI) and type II (T beta RII) receptors. To gain insight into the possible role of TGF-beta receptors in the pathogenesis of pulmonary fibrosis, we investigated the expression of TGF-beta receptors and their ligands in a bleomycin-induced model of pulmonary fibrosis. We found that the expression of both T beta RI and T beta RII was altered in rat lungs during pulmonary fibrosis induced by bleomycin. The increase in T beta RI mRNA level was evident after 3 days of bleomycin administration, and T beta RI mRNA continually increased for over 12 days after bleomycin instillation, whereas T beta RII mRNA declined at day 3 post bleomycin instillation and then increased during the reparative phase of lung injury (days 8 and 12). The immunoreactivity for both T beta RI and T beta RII was detected in the cells of the interstitium, the epithelium, and the blood vessels of normal rat lungs. In bleomycin-induced pulmonary fibrosis, an extensive immunostaining for T beta RI and T beta RII was present in the cells at the sites of injury and active fibrosis. These results demonstrate that the expression of TGF-beta type I and type Il receptors was altered during pulmonary fibrosis, suggesting that the TGF-beta signal transduction pathway may be involved in the pathogenesis of lung fibrosis. (C) 2000 Academic Press.
引用
收藏
页码:67 / 78
页数:12
相关论文
共 55 条
[1]   PLATELET-DERIVED GROWTH-FACTOR IN IDIOPATHIC PULMONARY FIBROSIS [J].
ANTONIADES, HN ;
BRAVO, MA ;
AVILA, RE ;
GALANOPOULOS, T ;
NEVILLEGOLDEN, J ;
MAXWELL, M ;
SELMAN, M .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (04) :1055-1064
[2]   IDENTIFICATION OF HUMAN ACTIVIN AND TGF-BETA TYPE-I RECEPTORS THAT FORM HETEROMERIC KINASE COMPLEXES WITH TYPE-II RECEPTORS [J].
ATTISANO, L ;
CARCAMO, J ;
VENTURA, F ;
WEIS, FMB ;
MASSAGUE, J ;
WRANA, JL .
CELL, 1993, 75 (04) :671-680
[3]   TRANSFORMING GROWTH FACTOR-BETA-1 IS PRESENT AT SITES OF EXTRACELLULAR-MATRIX GENE-EXPRESSION IN HUMAN PULMONARY FIBROSIS [J].
BROEKELMANN, TJ ;
LIMPER, AH ;
COLBY, TV ;
MCDONALD, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) :6642-6646
[4]  
CHANDLER DB, 1983, AM J PATHOL, V112, P170
[5]   INACTIVATION OF THE TYPE-II RECEPTOR REVEALS 2 RECEPTOR PATHWAYS FOR THE DIVERSE TGF-BETA ACTIVITIES [J].
CHEN, RH ;
EBNER, R ;
DERYNCK, R .
SCIENCE, 1993, 260 (5112) :1335-1338
[6]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[7]   Diverse cellular TGF-beta(1) and TGF-beta(3) gene expression in normal human and murine lung [J].
Coker, RK ;
Laurent, GJ ;
Shahzeidi, S ;
HernandezRodriguez, NA ;
Pantelidis, P ;
duBois, RM ;
Jeffery, PK ;
McAnulty, RJ .
EUROPEAN RESPIRATORY JOURNAL, 1996, 9 (12) :2501-2507
[8]   PATHOBIOLOGY OF PULMONARY FIBROSIS [J].
CROUCH, E .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (04) :L159-L184
[9]   Cloning by Polymerase Chain Reaction of a New Mouse TGF-beta, mTGF-beta 3 [J].
Denhez, Fabienne ;
Lafyatis, Robert ;
Kondaiah, Paturu ;
Roberts, Anita B. ;
Sporn, Michael B. .
GROWTH FACTORS, 1990, 3 (02) :139-146
[10]   Intracellular signalling: The Mad way to do it [J].
Derynck, R ;
Zhang, Y .
CURRENT BIOLOGY, 1996, 6 (10) :1226-1229