Expression of TGF-β receptors type I and II in human glomerulonephritis

Abstract

Background. Transforming growth factor-β (TGF-β) is a multipotent cytokine involved in the turnover of the extracellular matrix. Signal transduction of TGF-β 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-β and its receptors RI and RII in human glomerulonephritis. Methods. Indirect immunofluorescence using monoclonal and polyclonal antibodies against TGF-β isoforms (1,2,3 and 2,3), TGFβ-RI and TGFβ-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-β 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-β-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-β 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-β and its ligand may represent a critical factor conditioning the tissue response to immunological injury.