Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis

Hashimoto, Toko; Yasuda, Shinsuke; Koide, Hideyuki et al.

Arthritis Research & Therapy, 2011, 13(5), R154

Permalink : https://hdl.handle.net/2115/48856

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アクセス権
open access
URI
https://hdl.handle.net/2115/48856
タイトル
Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis
著者
Hashimoto, Toko ; Yasuda, Shinsuke ; Koide, Hideyuki ; Kataoka, Hiroshi ; Horita, Tetsuya ; Atsumi, Tatsuya ; Koike, Takao
著者名
Hashimoto, Toko
e-Rad_Researcher
00374231
著者名
Yasuda, Shinsuke
著者名
Koide, Hideyuki
著者名
Kataoka, Hiroshi
著者名
Horita, Tetsuya
著者名
Atsumi, Tatsuya
e-Rad_Researcher
80146795
著者名
Koike, Takao
言語
英語
発行日
2011-09-20
出版者
BioMed Central
収録物名
Arthritis Research & Therapy
巻(号)
13(5)
ページ
R154
抄録
Introduction: An unidentified population of peripheral blood mononuclear cells (PBMCs) express Ras guanine nucleotide releasing protein 4 (RasGRP4). The aim of our study was to identify the cells in human blood that express hRasGRP4, and then to determine if hRasGRP4 was altered in any patient with rheumatoid arthritis (RA). Methods: Monocytes and T cells were purified from PBMCs of normal individuals, and were evaluated for their expression of RasGRP4 mRNA/protein. The levels of RasGRP4 transcripts were evaluated in the PBMCs from healthy volunteers and RA patients by real-time quantitative PCR. The nucleotide sequences of RasGRP4 cDNAs were also determined. RasGRP4 protein expression in PBMCs/monocytes was evaluated. Recombinant hRasGRP4 was expressed in mammalian cells. Results: Circulating CD14+ cells in normal individuals were found to express hRasGRP4. The levels of the hRasGRP4 transcript were significantly higher in the PBMCs of our RA patients relative to healthy individuals. Sequence analysis of hRasGRP4 cDNAs from these PBMCs revealed 10 novel splice variants. Aberrantly spliced hRasGRP4 transcripts were more frequent in the RA patients than in normal individuals. The presence of one of these abnormal splice variants was linked to RA. The levels of hRasGRP4 protein in PBMCs tended to be lower. As expected, the defective transcripts led to altered and/or nonfunctional protein in terms of P44/42 mitogen-activated protein (MAP) kinase activation. Conclusions: The identification of defective isoforms of hRasGRP4 transcripts in the PBMCs of RA patients raises the possibility that dysregulated expression of hRasGRP4 in developing monocytes plays a pathogenic role in a subset of RA patients.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 2.0 Generic
PISSN
1478-6354
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1186/ar3470