Kidney Expression of RhoA, TGF-(beta)_1, and Fibronectin in Human IgA Nephropathy

摘要

Background: The Rho/transforming growth factor-beta (TGF-beta) system plays a crucial role in the progression of renal damage due to stimulation of extracellular matrix molecule deposition. In fact, the in vitro TGF-beta-mediated production of fibronectin, one of the major TGF-beta-regulated extracellular components, has recently been correlated with Rho protein signalling molecules. Although a close relationship between increased renal tissue levels of TGF-beta1 and fibronectin has been reported in IgA nephropathy, no data are available on renal tissue expression of Rho proteins. Methods: This study was designed to assess in IgA nephropathy patients the kidney tissue immunohistochemical expression of RhoA, TGF-(31, and fibronectin, and the rate of immunoreactivity for each antigen by image analysis. Results: An increase in RhoA, TGF-beta1, and fibronectin expression was detected in tubulointerstitium and in glomeruli of IgA nephropathy compared to normal kidneys; in particular, RhoA was found also in proximal tubules, unlike control kidneys and mainly at the cell boundary level, which is in keeping with its activated form. The image analysis confirmed that the kidney tissue levels of RhoA, TGF-beta1, and fibronectin were significantly enhanced in the patients. Conclusion: This study suggests that RhoA may represent a key molecule in the signalling transduction pathway of profibrotic signals in IgA nephropathy.