Induction and Coexpression of Latent Transforming Growth Factor β-Binding Protein-1 and Fibrillin-1 in Experimental Glomerulonephritis

Background: Latent transforming growth factor-β-binding protein 1 (LTBP-1) and fibrillin-1 were shown to colocalize and interact in the extracellular matrix of the skin and vasculature. This interaction may regulate transforming growth factor-β (TGF-β ) activity. TGF-β is an important progression factor for glomerular diseases. We hypothesized that LTBP-1 and fi brillin-1 are coexpressed in the glomerulus and upregulated during glomerulonephritis. Methods: Acute anti-Thy1.1 glomerulonephritis was induced with a single intravenous injection (1 mg/kg body weight) of a monoclonal anti-Thy1.1 antibody in rats. Real-time RT-PCR and immunohistochemical analyses for LTBP-1 and fi brillin-1 were performed. Results: Induction of glomerular LTBP-1 mRNA was detected on day 2 of disease, while mRNA for fi brillin-1 was already upregulated 1 day after induction of disease. Both LTBP- 1 and fi brillin-1 showed a mesangial distribution. An expansion of the LTBP-1 and fi brillin-1-positive mesangial area was seen on day 6 of disease, when transient matrix accumulation was most prominent. On day 12 of disease, glomerular LTBP-1 and fi brillin-1 immunoreactivities had returned to control levels. In serial sections, some colocalization of LTBP-1 and fi brillin-1 was detected in control as well as in nephritic glomeruli. Conclusion: Mesangial expression of LTBP-1 and fi brillin-1 is induced early in experimental nephritis and LTBP-1 and fi brillin-1 are partially colocalized in the nephritic glomerulus. An interaction of these molecules could stabilize latent TGF-β complexes and thus attenuate the activation of TGF- β during this self-limited glomerular disease