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.
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.


CONCLUSIONS
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.
Han
Sang-Youb
SY
Department of Internal Medicine, Inje University College of Medicine, Go-yang, Korea.
Ihm
Chun-Gyoo
CG
Cha
Dae-Ryong
DR
Kang
Young-Sun
YS
Han
Kum-Hyun
KH
Kim
Hyoung-Kyu
HK
Han
Jee-Young
JY
D002478:Cells, Cultured; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D007070:Immunoglobulin A; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1