TLR9型
肾病
免疫学
医学
Toll样受体
肾小球肾炎
肾脏疾病
受体
单核苷酸多态性
自身免疫
抗原
生物
免疫系统
内科学
先天免疫系统
肾
基因
内分泌学
基因表达
基因型
遗传学
DNA甲基化
糖尿病
作者
Hitoshi Suzuki,Yusuke Suzuki,Ichiei Narita,Masashi Aizawa,Masao Kihara,Takahiro Yamanaka,Tatsuya Kanou,Hiroyasu Tsukaguchi,Jan Novák,Satoshi Horikoshi,Yasuhiko Tomino
出处
期刊:Journal of The American Society of Nephrology
日期:2008-12-01
卷期号:19 (12): 2384-2395
被引量:155
标识
DOI:10.1681/asn.2007121311
摘要
Environmental pathogens are suspected to aggravate renal injury in IgA nephropathy (IgAN), but neither underlying mechanisms nor specific exogenous antigens have been identified. In this study, a genome-wide scan of ddY mice, which spontaneously develop IgAN, was performed, and myeloid differentiation factor 88 (MyD88) was identified as a candidate gene for progression of renal injury (chi(2) = 21.103, P = 0.00017). For evaluation of the potential influence of environmental pathogens on progression of renal injury, ddY mice were housed in either conventional or specific pathogen-free conditions. Expression of genes encoding toll-like receptors (TLR) and the signaling molecule MyD88 were quantified by real-time reverse transcription-PCR in splenocytes. Although the housing conditions did not affect the prevalence of IgAN, the severity of renal injuries was higher in the conventionally housed group. Mice that had IgAN and were housed in conventional conditions had higher levels of TLR9 and MyD88 transcripts than mice that had IgAN and were housed in specific pathogen-free conditions. Furthermore, nasal challenge with CpG-oligodeoxynucleotides, which are ligands for TLR9, aggravated renal injury, led to strong Th1 polarization, and increased serum and mesangial IgA. For investigation of whether these results may be generalizable to humans, single-nucleotide polymorphisms in the TLR9 and MyD88 genes were analyzed in two cohorts of patients with IgAN; an association was observed between TLR9 polymorphisms and disease progression. In summary, these findings suggest that activation of the TLR9/MyD88 pathway by common antigens may affect the severity of IgAN.
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