Effect of IgA aggregates on transforming growth factor-β1 production in human mesangial cells and the intraglomerular expression of transforming growth factor-β1 in patients with IgA nephropathy

Abstract

Background: Transforming growth factor-β (TGF-β) stimulates renal fibrosis in various renal diseases including IgA nephropathy. Methods: We examined whether immunoglobulin A (IgA) stimulated TGF-β1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-β mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. Results: The IgA aggregate increased the TGF-β1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-β1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-β1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=-0.809, p=0.015). Glomerular TGF-β1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-β1 mRNA showed a tendency for an decrease of their renal function. Conclusion: The IgA aggregate increased TGF-β1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-β1 mRNA expression could be useful in predicting the progression of IgA nephropathy.