Role of TGF-β1 in renal parenchymal scarring following childhood urinary tract infection

被引:55
作者
Cotton, SA
Gbadegesin, RA
Williams, S
Brenchley, PEC
Webb, NJA
机构
[1] Manchester Royal Infirm, Renal Res Labs, Manchester Inst Nephrol & Transplantat, Manchester M13 9WL, Lancs, England
[2] Royal Manchester Childrens Hosp, Dept Nephrol, Manchester M27 1HA, Lancs, England
关键词
pediatric nephropathy; transforming growth factor-beta 1; polymorphisms; -800 GA genotype; fibrosis; bacterial infection;
D O I
10.1046/j.1523-1755.2002.00110.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Significant variability exists in the outcome of renal parenchymal inflammation following urinary tract infection (UTI) in childhood as some children experience renal parenchymal scarring (RPS) while others do not scar. Since TGF-beta1 is pro-fibrotic, we examined the role of this cytokine in RPS following UTI. Methods. Five polymorphisms of the TGF-PI gene were investigated as well as the relationship between these polymorphisms and TGF-beta1 production by peripheral blood mononuclear cells (PBMC) in vitro. DNA was isolated from 91 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI, and 171 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP). PBMC were isolated from a subgroup of 24 patients from the total population. Cells were stimulated with LPS + PMA + PHA and then TGF-beta1 production was determined by ELISA. Results. Comparing the NS with the RPS group, there was an increase in the -800 GA genotypes (18.6 vs. 7.4%, P = 0.05; chi (2)) and the Leu(10)--> Pro CT (62.8 vs. 41.5%, P = 0.021), and a decrease in the -509 TT genotype (0.0 vs. 8.5%, P = 0.049). PBMC TGF-beta1 production was higher in those patients with the -800 GG compared to those with a GA genotype stimulation index [stimulated/unstimulated TGF-beta1 levels were 1.54 interquartile range (IQR) 1.42 to 1.75 vs. 1.19, IQR 0.94 to 1.51, P = 0.031]. Conclusions. There is an association between the TGF-beta1 -800 GA, -509 TT and Leu(10)-Pro CT genotypes and the presence or absence of RPS. The low TGF-beta1 producer status of the -800 GA genotype may protect against the development of a pro-fibrotic pathology.
引用
收藏
页码:61 / 67
页数:7
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