Home LiteratureArticle Details
PMID: 2200803 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix.

The Journal of clinical investigation ·Vol. 86 ·No. 2 ·1990-08-00 ·Pages 453-62

Okuda S, Languino LR, Ruoslahti E, Border WA

Abstract

Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological extracellular matrix in glomerulonephritis.

MeSH Terms
Animals Antilymphocyte Serum/pharmacology Blotting, Northern Culture Techniques Extracellular Matrix/metabolism Fibronectins/biosynthesis Fluorescent Antibody Technique Glomerular Mesangium/metabolism Glomerulonephritis/metabolism,pathology Microscopy, Electron Proteoglycans/biosynthesis RNA, Messenger/genetics Rats Transforming Growth Factors/genetics,metabolism
Chemicals
Antilymphocyte Serum Fibronectins Proteoglycans RNA, Messenger Transforming Growth Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Okuda S
Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132.
Languino L R
Ruoslahti E
Border W A
References (50)
50 references, click to expand
  1. Cell adhesion protein receptors as targets for transforming growth factor-beta action.
    Cell. 1987 Oct 23;51(2):189-97 PMID: 3499229
  2. Transforming growth factor-beta induction of type-1 plasminogen activator inhibitor. Pericellular deposition and sensitivity to exogenous urokinase.
    J Biol Chem. 1987 Dec 25;262(36):17467-74 PMID: 3121597
  3. Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat.
    Kidney Int. 1987 Oct;32(4):514-25 PMID: 2892961
  4. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans.
    J Biol Chem. 1988 Feb 25;263(6):3039-45 PMID: 3422640
  5. Antibodies to peptide determinants in transforming growth factor beta and their applications.
    Biochemistry. 1988 Jan 26;27(2):739-46 PMID: 2450577
  6. 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
  7. The progression of renal disease.
    N Engl J Med. 1988 Jun 23;318(25):1657-66 PMID: 3287163
  8. 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
  9. Transforming growth factor beta regulates the metabolism of proteoglycans in bovine cartilage organ cultures.
    J Biol Chem. 1988 Sep 15;263(26):12828-31 PMID: 3166454
  10. Increased tumor necrosis factor and IL-1 beta gene expression in the kidneys of mice with lupus nephritis.
    J Immunol. 1988 Nov 1;141(9):3050-4 PMID: 3262676
  11. Distinguishing minimal-change disease from mesangial disorders.
    Kidney Int. 1988 Sep;34(3):419-34 PMID: 3050250
  12. cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence for alternate splicing and polyadenylation.
    J Biol Chem. 1988 Dec 5;263(34):18313-7 PMID: 2461367
  13. Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation.
    Nature. 1988 Nov 17;336(6196):244-6 PMID: 3194009
  14. Structure and biology of proteoglycans.
    Annu Rev Cell Biol. 1988;4:229-55 PMID: 3143379
  15. Transforming growth factor beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis.
    Recent Prog Horm Res. 1988;44:157-97 PMID: 3064207
  16. Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes.
    J Cell Biol. 1989 Feb;108(2):653-60 PMID: 2465297
  17. Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species.
    J Biol Chem. 1989 Mar 15;264(8):4571-6 PMID: 2647739
  18. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells.
    J Clin Invest. 1989 Apr;83(4):1160-7 PMID: 2539392
  19. Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon.
    Biochem J. 1984 Nov 1;223(3):587-97 PMID: 6439184
  20. Improved methods for culturing rat glomerular cells.
    Kidney Int. 1984 Dec;26(6):875-80 PMID: 6533398
  21. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family.
    Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 PMID: 2987824
  22. The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors.
    Ann Surg. 1986 Feb;203(2):142-7 PMID: 3511865
  23. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.
    J Biol Chem. 1986 Mar 25;261(9):4337-45 PMID: 3456347
  24. 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
  25. Transforming growth factor-beta: biological function and chemical structure.
    Science. 1986 Aug 1;233(4763):532-4 PMID: 3487831
  26. Cell culture approaches to the analysis of glomerular inflammation.
    Kidney Int. 1986 Aug;30(2):246-54 PMID: 3531678
  27. Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA.
    Proc Natl Acad Sci U S A. 1986 Oct;83(20):7683-7 PMID: 3484330
  28. Glomerulonephritis induced by monoclonal anti-Thy 1.1 antibodies. A sequential histological and ultrastructural study in the rat.
    Lab Invest. 1986 Dec;55(6):680-7 PMID: 3537521
  29. The TGF-beta family of growth and differentiation factors.
    Cell. 1987 May 22;49(4):437-8 PMID: 3471351
  30. The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis.
    J Immunol. 1987 May 15;138(10):3207-12 PMID: 2883234
  31. Interaction of small dermatan sulfate proteoglycan from fibroblasts with fibronectin.
    J Cell Biol. 1987 Jun;104(6):1683-91 PMID: 3584245
  32. Complement dependence of antibody-induced mesangial cell injury in the rat.
    J Immunol. 1987 Jun 1;138(11):3758-65 PMID: 3495569
  33. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5287-91 PMID: 3474655
  34. Distribution and modulation of the cellular receptor for transforming growth factor-beta.
    J Cell Biol. 1987 Aug;105(2):965-75 PMID: 2887577
  35. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.
    EMBO J. 1987 Jul;6(7):1899-904 PMID: 2820711
  36. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.
    J Cell Biol. 1989 Jun;108(6):2477-82 PMID: 2500447
  37. Alterations in the extracellular matrix components in human glomerular diseases.
    Virchows Arch A Pathol Anat Histopathol. 1989;415(2):151-9 PMID: 2500770
  38. Platelets mediate glomerular cell proliferation in immune complex nephritis induced by anti-mesangial cell antibodies in the rat.
    Am J Pathol. 1990 Feb;136(2):369-74 PMID: 1968315
  39. Transforming growth factor-beta regulates production of proteoglycans by mesangial cells.
    Kidney Int. 1990 Feb;37(2):689-95 PMID: 2407884
  40. Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex.
    Growth Factors. 1989;1(3):203-18 PMID: 2629880
  41. Isolation of a plasma-membrane subfraction from rat liver containing an insulin-sensitive cyclic-AMP phosphodiesterase.
    Eur J Biochem. 1972 Jan 21;24(3):429-37 PMID: 4333651
  42. Failure of heparin to affect two types of experimental glomerulonephritis in rabbits.
    Kidney Int. 1975 Sep;8(3):140-8 PMID: 126330
  43. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  44. Fibronectin localization in the rat glomerulus.
    J Cell Biol. 1980 Dec;87(3 Pt 1):691-6 PMID: 7007395
  45. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen.
    J Clin Invest. 1982 Feb;69(2):451-61 PMID: 7056856
  46. Comparative distribution of laminin, type IV collagen, and fibronectin in the rat glomerulus.
    J Histochem Cytochem. 1982 Sep;30(9):874-86 PMID: 7130672
  47. Purification and properties of a type beta transforming growth factor from bovine kidney.
    Biochemistry. 1983 Dec 6;22(25):5692-8 PMID: 6607069
  48. Biophysiology of glomerular filtration and proteinuria.
    Lab Invest. 1984 Jul;51(1):7-21 PMID: 6376945
  49. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts.
    J Biol Chem. 1984 Sep 10;259(17):10995-1000 PMID: 6088525
  50. Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats.
    Kidney Int. 1984 Aug;26(2):137-43 PMID: 6239058
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114731
Published
1990-08-00
Pages
453-62
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC296747
Subset
IM
Grants
PHS HHS · 30199 · United States
NCI NIH HHS · CA 28896 · United States
NCI NIH HHS · CA 42507 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1172/JCI114731 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2