Expression of TGF-beta receptors type I and II in human glomerulonephritis.
BACKGROUND
Transforming growth factor-beta (TGF-beta) is a multipotent cytokine involved in the turnover of the extracellular matrix. Signal transduction of TGF-beta is regulated via at least five different surface receptors; most of the effects, however, are mediated through the interaction of receptors type I and II (RI and RII). We investigated the glomerular expression of TGF-beta and its receptors RI and RII in human glomerulonephritis.


METHODS
Indirect immunofluorescence using monoclonal and polyclonal antibodies against TGF-beta isoforms (1,2,3 and 2,3), TGF beta-RI and TGF beta-RII has been carried out on 30 consecutive renal biopsies (5 FSGS, 11 IgAN, 4 MCGN, 6 SLE, 2 RPGN) and on normal kidney tissue.


RESULTS
Glomerular immunoreactivity for TGF-beta isoforms correlated with the severity of proliferative lesions: immunofluorescent signal was absent or trace-like in normal kidneys, FSGS, and IgAN with mild mesangial cellularity, and was highest in IgAN with severe mesangial proliferation, MPGN, RPGN, and SLE. Glomerular positivity for TGF-beta-RI and -RII was detectable in SLE and RPGN; a low signal was present also in MPGN. Other types of glomerulonephritis, including focal extracapillary proliferations, and glomeruli of normal kidneys were always negative.


CONCLUSIONS
Our data show that TGF-beta expression is a good indicator of the severity of proliferative glomerular lesions in most, if not all cases and that RI-RII expression occurs at levels detectable with indirect immunofluorescence in limited number of glomerulonephritides, mostly associated with systemic diseases. A complex interaction between TGF-beta and its ligand may represent a critical factor conditioning the tissue response to immunological injury.
Onetti Muda
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A
Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Rome, Italy.
Feriozzi
S
S
Rahimi
S
S
Faraggiana
T
T
D019084:Fluorescent Antibody Technique, Indirect; D005921:Glomerulonephritis / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D007668:Kidney / Q000378:metabolism; D008181:Lupus Nephritis / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012016:Reference Values
D018125:Receptors, Transforming Growth Factor beta