Korean J Intern Med.
2005 Mar;20(1):40-47. 10.3904/kjim.2005.20.1.40.
Effect of IgA Aggregates on Transforming Growth Factor-beta1 Production in Human Mesangial Cells and the Intraglomerular Expression of Transforming Growth Factor-beta1 in Patients with IgA Nephropathy
- Affiliations
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- 1Department of Internal Medicine, Inje University College of Medicine, Go-yang, Korea.
- 2Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
- 3Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea. cdragn@unitel.co.kr
- 4Department of Pathology, College of Medicine, Inha University, Incheon, Korea.
- KMID: 1776695
- DOI: http://doi.org/10.3904/kjim.2005.20.1.40
Abstract
- BACKGROUND
Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 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-beta1 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-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 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-beta1 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-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
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