記事の詳細

ヒト染色体1q21.1上のS100遺伝子クラスターのおよそ半分は
リウマチ, SLE, polyJIA, sJIA患者の血中で、その遺伝子発現が増加している。

About half of S100 cluster genes on chromosome 1q21.1 are up-regulated in the RA, SLE, polyarticular type juvenile idiopathic arthritis (polyJIA), and systemic-onset JIA (sJIA).

○Hidehiko Sugino(杉野英彦)1, Chieko Aoki2, Hooi-Ming Lee1, Yasuo Adachi2, Kenichi Matsubara3 and Takahiro Ochi4 and Norihiro Nishimoto1, 2.

1. Graduate School of Frontier Biosciences, Osaka University
2. Laboratory of Immune Regulation, Wakayama Medical University
3. DNA Chip Research Inc., Yokohama, Japan
4. Osaka Police Hospital

Background
S100 gene family encodes the EF-hand super-family of calcium binding proteins including at least 14 family members clustered relatively closely on chromosome 1q21.1. Recently, up-regulation of S100 proteins, S100A4, A8/9 and A12, in RA patients has been reported.
Objective
To know the pathological roles of S100 proteins, we investigated the comprehensive gene expression profiling of 17 kinds of S100 proteins using DNA microarray in patients with active RA, SLE, polyJIA, and sJIA. These 17 kinds of S100 proteins contain the clustered 14 molecules. Moreover, to clarify the molecular functions of S100 proteins in RA, we compared the amino acid sequence of up-regulated S100 proteins.
Methods
Total RNA was extracted from the peripheral blood obtained from 114 patients with RA, 12 patients with SLE, 6 patients with polyJIA, 51 patients with sJIA, and 53 healthy individuals, and used to prepare amino allylRNA (aRNA). aRNA was subjected to Cy3 and Cy5 labeling and hybridized with an oligonucleotide-based DNA microarray. The data among patients and healthy individuals were analyzed by parametric statistical group comparison. The amino acid sequences of S100 proteins were aligned by multi-sequence Clustal X analysis. Evolutionary trees were obtained by NJ analysis (1000 bootstrap).
Results
S100A4, A6, A8/9, A11 and A12 are significantly up-regulated in RA and polyJIA compared to healthy controls. S100A6, A8/9, A11 and A12 were also up-regulated in SLE and sJIA. S100A4 was increased in the groups of RA and polyJIA but not in the groups of SLE and sJIA. Except for these six S100 proteins, other eleven S100 proteins remained stationary among the RA, SLE, sJIA, polyJIA and healthy controls. Phylogenetic tree of S100 proteins shows that the S100A8/9 and A12, which have been frequently reported in inflammation, recently branched off from the same origin and average percent similarity is 74.3 %. In contrast, S100A4, A6 and A11 are diversified with each other in the amino acid levels.
Conclusion
We confirmed the up-regulation of S100A4, A8/9 and A12 in RA and newly found the up-regulation of S100A6 and A11 in RA, SLE, polyJIA and sJIA. All the genes are encoded by human chromosome1q21.1. The structural similarities and diversifications among the 6 kinds of S100 proteins, which up-regulated in RA patients, may reflect the different contributions to the etiologies of RA.

リンク先
https://acr.confex.com/acr/2009/webprogram/ACRCC.html

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