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Elevated expression of transforming growth factor-β and proteoglycan production in experimental glomerulonephritis : possible role in expansion of the mesangial extracellular matrix

The Journal of clinical investigation, 1990-08, Vol.86 (2), p.453-462 [Peer Reviewed Journal]

1993 INIST-CNRS ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/jci114731 ;PMID: 2200803 ;CODEN: JCINAO

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  • Title:
    Elevated expression of transforming growth factor-β and proteoglycan production in experimental glomerulonephritis : possible role in expansion of the mesangial extracellular matrix
  • Author: OKUDA, S ; LANGUINO, L. R ; RUOSLAHTI, E ; BORDER, W. A
  • Subjects: Animals ; Antilymphocyte Serum - pharmacology ; Biological and medical sciences ; Blotting, Northern ; Culture Techniques ; Extracellular Matrix - metabolism ; Fibronectins - biosynthesis ; Fluorescent Antibody Technique ; Glomerular Mesangium - metabolism ; Glomerulonephritis - metabolism ; Glomerulonephritis - pathology ; Medical sciences ; Microscopy, Electron ; Nephrology. Urinary tract diseases ; Proteoglycans - biosynthesis ; Rats ; RNA, Messenger - genetics ; Transforming Growth Factors - genetics ; Transforming Growth Factors - metabolism
  • Is Part Of: The Journal of clinical investigation, 1990-08, Vol.86 (2), p.453-462
  • Description: 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.
  • Publisher: Ann Arbor, MI: American Society for Clinical Investigation
  • Language: English
  • Identifier: ISSN: 0021-9738
    EISSN: 1558-8238
    DOI: 10.1172/jci114731
    PMID: 2200803
    CODEN: JCINAO
  • Source: GFMER Free Medical Journals
    MEDLINE
    PubMed Central
    Alma/SFX Local Collection

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