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PMID: 9916924 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Active transforming growth factor-beta in wound repair: determination using a new assay.

The American journal of pathology ·Vol. 154 ·No. 1 ·1999-01-00 ·Pages 105-11

Yang L, Qiu CX, Ludlow A, Ferguson MW, Brunner G

Abstract

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 wounding). A second peak of active TGF-beta (17% of total) occurred at 5 days after wounding. The predominant isoforms were TGF-beta1 and -2 with only minor amounts of TGF-beta3 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.

MeSH Terms
Animals Biological Assay/methods Frozen Sections Hot Temperature Isomerism Male Rats Rats, Sprague-Dawley Recombinant Proteins Skin/injuries Transforming Growth Factor beta/metabolism,physiology Wound Healing/physiology Wounds, Penetrating/physiopathology
Chemicals
Recombinant Proteins Transforming Growth Factor beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yang L
Division of Cells, Immunology and Development, School of Biological Sciences, University of Manchester, United Kingdom.
Qiu C X
Ludlow A
Ferguson M W
Brunner G
References (54)
54 references, click to expand
  1. Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin.
    J Biol Chem. 1992 Dec 15;267(35):25378-84 PMID: 1281156
  2. Control of transforming growth factor-beta activity: latency vs. activation.
    Prog Growth Factor Res. 1992;4(4):321-35 PMID: 1340213
  3. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta.
    Lancet. 1992 Jan 25;339(8787):213-4 PMID: 1346175
  4. Basic fibroblast growth factor-induced activation of latent transforming growth factor beta in endothelial cells: regulation of plasminogen activator activity.
    J Cell Biol. 1992 Aug;118(4):901-9 PMID: 1380001
  5. Transforming growth factor-beta complexes with thrombospondin.
    Mol Biol Cell. 1992 Feb;3(2):181-8 PMID: 1550960
  6. Characterization of the activation of latent TGF-beta by co-cultures of endothelial cells and pericytes or smooth muscle cells: a self-regulating system.
    J Cell Biol. 1990 Aug;111(2):757-63 PMID: 1696270
  7. Wound healing in the fetus. Possible role for inflammatory macrophages and transforming growth factor-beta isoforms.
    Wound Repair Regen. 1994 Mar-Apr;2(2):104-12 PMID: 17134379
  8. Autocrine transforming growth factor-beta(1) activity and glycosaminoglycan synthesis by human cutaneous scar fibroblasts.
    Wound Repair Regen. 1994 Oct;2(4):284-91 PMID: 17147647
  9. The role of transforming growth factor-beta in the conversion from "scarless" healing to healing with scar formation.
    Wound Repair Regen. 1995 Apr-Jun;3(2):229-36 PMID: 17173652
  10. Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration.
    J Cell Biol. 1991 Jun;113(6):1439-45 PMID: 1828468
  11. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.
    Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6642-6 PMID: 1862087
  12. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy.
    N Engl J Med. 1991 Apr 4;324(14):933-40 PMID: 1900574
  13. Transforming growth factor beta type 1 binds to collagen IV of basement membrane matrix: implications for development.
    Dev Biol. 1991 Feb;143(2):303-8 PMID: 1991553
  14. Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model.
    J Invest Dermatol. 1991 Jul;97(1):34-42 PMID: 2056191
  15. The transforming growth factor-beta family.
    Annu Rev Cell Biol. 1990;6:597-641 PMID: 2177343
  16. Physicochemical activation of recombinant latent transforming growth factor-beta's 1, 2, and 3.
    Growth Factors. 1990;3(1):35-43 PMID: 2200452
  17. Negative regulation of transforming growth factor-beta by the proteoglycan decorin.
    Nature. 1990 Jul 19;346(6281):281-4 PMID: 2374594
  18. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1.
    Nature. 1990 Jul 26;346(6282):371-4 PMID: 2374609
  19. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
    Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 PMID: 2424019
  20. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta.
    Science. 1987 Sep 11;237(4820):1333-6 PMID: 2442813
  21. Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin.
    J Biol Chem. 1987 Oct 15;262(29):14090-9 PMID: 2443501
  22. Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta.
    J Cell Biol. 1989 Dec;109(6 Pt 1):3137-45 PMID: 2592419
  23. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788-92 PMID: 2886992
  24. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium.
    J Cell Biol. 1988 May;106(5):1659-65 PMID: 2967299
  25. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping.
    Science. 1988 Aug 5;241(4866):708-12 PMID: 3041594
  26. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization.
    J Biol Chem. 1988 May 5;263(13):6407-15 PMID: 3162913
  27. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences.
    J Biol Chem. 1988 Jun 5;263(16):7646-54 PMID: 3163692
  28. Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.
    J Pediatr Surg. 1988 Jul;23(7):647-52 PMID: 3204464
  29. Role of transforming growth factor-beta in the development of the mouse embryo.
    J Cell Biol. 1987 Dec;105(6 Pt 2):2861-76 PMID: 3320058
  30. Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.
    Proc Natl Acad Sci U S A. 1988 Jan;85(2):587-91 PMID: 3422443
  31. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells.
    J Cell Biol. 1986 Apr;102(4):1217-23 PMID: 3457014
  32. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets.
    Science. 1986 Sep 5;233(4768):1078-80 PMID: 3461562
  33. Fibronectin-associated transforming growth factor.
    J Cell Physiol. 1987 May;131(2):184-9 PMID: 3495542
  34. Transforming growth factor-beta 1 regulates axon/Schwann cell interactions.
    J Cell Biol. 1995 Apr;129(2):443-58 PMID: 7536747
  35. A human keratinocyte cell line produces two autocrine growth inhibitors, transforming growth factor-beta and insulin-like growth factor binding protein-6, in a calcium- and cell density-dependent manner.
    J Biol Chem. 1995 May 26;270(21):12373-9 PMID: 7539002
  36. Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring.
    J Cell Sci. 1995 Mar;108 ( Pt 3):985-1002 PMID: 7542672
  37. Release and activation of platelet latent TGF-beta in blood clots during dissolution with plasmin.
    Nat Med. 1995 Sep;1(9):932-7 PMID: 7585220
  38. Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein.
    J Cell Biol. 1995 Oct;131(2):539-49 PMID: 7593177
  39. Characterization of latent TGF-beta activation by murine peritoneal macrophages.
    J Immunol. 1995 Aug 1;155(3):1450-9 PMID: 7636210
  40. Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents.
    J Cell Sci. 1994 May;107 ( Pt 5):1137-57 PMID: 7929624
  41. Transforming growth factor beta in tissue fibrosis.
    N Engl J Med. 1994 Nov 10;331(19):1286-92 PMID: 7935686
  42. Activation of transforming growth factor-beta is inhibited in transgenic apolipoprotein(a) mice.
    Nature. 1994 Aug 11;370(6489):460-2 PMID: 8047165
  43. An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.
    Anal Biochem. 1994 Feb 1;216(2):276-84 PMID: 8179182
  44. Enhanced expression of mRNA for transforming growth factor-beta, type I and type III procollagen in human post-burn hypertrophic scar tissues.
    J Lab Clin Med. 1993 Oct;122(4):465-73 PMID: 8228562
  45. Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein.
    J Cell Biol. 1994 Jan;124(1-2):171-81 PMID: 8294500
  46. Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism.
    J Cell Biol. 1993 Aug;122(4):923-32 PMID: 8349738
  47. Transforming growth factor-beta: latent forms, binding proteins and receptors.
    Growth Factors. 1993;8(1):11-22 PMID: 8383513
  48. Mechanism of retinoid-induced activation of latent transforming growth factor-beta in bovine endothelial cells.
    J Cell Physiol. 1993 May;155(2):323-32 PMID: 8482724
  49. Prognostic significance of TGF-beta 1 and TGF-beta 2 expressions in female breast cancer.
    Anticancer Res. 1995 Nov-Dec;15(6B):2627-31 PMID: 8669837
  50. TGF-beta 1 stimulates cultured human fibroblasts to proliferate and produce tissue-like fibroplasia: a fibronectin matrix-dependent event.
    J Cell Physiol. 1997 Jan;170(1):69-80 PMID: 9012786
  51. Transforming growth factor beta s and wound healing.
    Int J Biochem Cell Biol. 1997 Jan;29(1):63-78 PMID: 9076942
  52. Quantification of transforming growth factor-beta in biological material using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.
    Anal Biochem. 1997 Apr 5;247(1):45-51 PMID: 9126369
  53. Latent transforming growth factor-beta: structural features and mechanisms of activation.
    Kidney Int. 1997 May;51(5):1376-82 PMID: 9150447
  54. Transforming growth factor-beta in breast cancer: a working hypothesis.
    Breast Cancer Res Treat. 1997 Aug;45(1):81-95 PMID: 9285120
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/s0002-9440(10)65256-x
Published
1999-01-00
Pages
105-11
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1868600
Subset
IM
External Links
PubMed source DOI: 10.1016/s0002-9440(10)65256-x PMC Full Text View journal details
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