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.
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 humanglomerulonephritis. 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.
Authors: Joost F M Lensen; Johan van der Vlag; Elly M M Versteeg; Jack F M Wetzels; Lambert P W J van den Heuvel; Jo H M Berden; Toin H van Kuppevelt; Angelique L W M M Rops Journal: PLoS One Date: 2015-08-31 Impact factor: 3.240