イシカワ　ゲン   ISHIKAWA Gen   石川　源    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes.
掲載誌名	正式名：Biology of reproduction 略　 称：Biol Reprod ISSNコード：15297268/00063363
掲載区分	国外
巻・号・頁	81(4),pp.717-729
著者・共著者	Shan-Shun Luo, Osamu Ishibashi, Gen Ishikawa, Tomoko Ishikawa, Akira Katayama, Takuya Mishima, Takami Takizawa, Takako Shigihara, Tadashi Goto, Akio Izumi, Akihide Ohkuchi, Shigeki Matsubara, Toshiyuki Takeshita, Toshihiro Takizawa
担当区分	筆頭著者
発行年月	2009/10
概要	In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A. Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.
DOI	10.1095/biolreprod.108.075481
PMID	19494253