Active transforming growth factor-β in wound repair -: Determination using a new assay

被引:78
作者
Yang, LJ [1 ]
Qiu, CX [1 ]
Ludlow, A [1 ]
Ferguson, MWJ [1 ]
Brunner, G [1 ]
机构
[1] Univ Manchester, Sch Biol Sci, Div Cells Immunol & Dev, Manchester M13 9PT, Lancs, England
关键词
D O I
10.1016/S0002-9440(10)65256-X
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Transforming growth factor (TGF)-beta regulates wound repair and scarring in an isoform-specific fashion. TGF-beta is produced in, a latent form, and its activation is a critical regulatory step controlling the bioactivity of this growth factor. To date, it has been impossible to determine latent TGF-beta activation in vivo due to a lack of quantitative assays. We describe here a semiquantitative modification of the plasminogen activator inhibitor-1/luciferase bioassay (PAI/L assay) for TGF-beta, which we used to determine active and latent TGF-beta isoforms in frozen sections of rat wound tissue. We found that significant amounts of latent TGF-beta were rapidly activated upon wounding (38% of the total TGF-beta at 1 hour after mounding). A second peak of active TGF-beta (17% of total) occurred at 5 days after wounding. The predominant isoforms were TGF-beta 1 and -2 with only minor amounts of TGF-beta 3 present. This is the first TGF-beta bioassay allowing semiquantitative determination of active and latent isoforms present in vivo, and our results document the significance and temporal regulation of latent TGF-beta isoform activation in wound repair.
引用
收藏
页码:105 / 111
页数:7
相关论文
共 58 条
[1]   AN ASSAY FOR TRANSFORMING GROWTH-FACTOR-BETA USING CELLS TRANSFECTED WITH A PLASMINOGEN-ACTIVATOR INHIBITOR-1 PROMOTER LUCIFERASE CONSTRUCT [J].
ABE, M ;
HARPEL, JG ;
METZ, CN ;
NUNES, I ;
LOSKUTOFF, DJ ;
RIFKIN, DB .
ANALYTICAL BIOCHEMISTRY, 1994, 216 (02) :276-284
[2]   MEMBRANE-ANCHORED AND SOLUBLE FORMS OF BETAGLYCAN, A POLYMORPHIC PROTEOGLYCAN THAT BINDS TRANSFORMING GROWTH FACTOR-BETA [J].
ANDRES, JL ;
STANLEY, K ;
CHEIFETZ, S ;
MASSAGUE, J .
JOURNAL OF CELL BIOLOGY, 1989, 109 (06) :3137-3145
[3]   TYPE-BETA TRANSFORMING GROWTH-FACTOR IN HUMAN-PLATELETS - RELEASE DURING PLATELET DEGRANULATION AND ACTION ON VASCULAR SMOOTH-MUSCLE CELLS [J].
ASSOIAN, RK ;
SPORN, MB .
JOURNAL OF CELL BIOLOGY, 1986, 102 (04) :1217-1223
[4]  
Auvinen P, 1995, ANTICANCER RES, V15, P2627
[5]   SUPPRESSION OF EXPERIMENTAL GLOMERULONEPHRITIS BY ANTISERUM AGAINST TRANSFORMING GROWTH FACTOR-BETA-1 [J].
BORDER, WA ;
OKUDA, S ;
LANGUINO, LR ;
SPORN, MB ;
RUOSLAHTI, E .
NATURE, 1990, 346 (6282) :371-374
[6]  
BORDER WA, 1994, NEW ENGL J MED, V331, P1286
[7]   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
[8]   Physicochemical Activation of Recombinant Latent Transforming Growth Factor-beta's 1, 2, and 3 [J].
Brownh, Peter D. ;
Wakefiel, Lalage M. ;
Levinson, Arthur D. ;
Sporn, Michael B. .
GROWTH FACTORS, 1990, 3 (01) :35-43
[9]   TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-ALPHA IN CHRONIC LIVER-DISEASE - EFFECTS OF INTERFERON ALFA THERAPY [J].
CASTILLA, A ;
PRIETO, J ;
FAUSTO, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (14) :933-940
[10]  
Clark R., 1996, Mezhdunarodnyi Sel'skokhozyaistvennyi Zhurnal, P3