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.
10.3904/kjim.2005.20.1.40
- Author:
Sang Youb HAN
1
;
Chun Gyoo IHM
;
Dae Ryong CHA
;
Young Sun KANG
;
Kum Hyun HAN
;
Hyoung Kyu KIM
;
Jee Young HAN
Author Information
1. Department of Internal Medicine, Inje University College of Medicine, Go-yang, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
IgA nephropathy;
IgA;
Transforming growth factor beta;
Competitive RT-PCR
- MeSH:
Cells, Cultured;
Female;
Glomerular Mesangium/*cytology/metabolism;
Glomerulonephritis, IGA/metabolism/pathology;
Humans;
Immunoglobulin A/*pharmacology;
Male;
Proteins/*metabolism;
RNA, Messenger/*metabolism;
Research Support, Non-U.S. Gov't
- From:The Korean Journal of Internal Medicine
2005;20(1):40-47
- CountryRepublic of Korea
- Language:English
-
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.
