オカノ　テルオ   Okano Teruo   岡野　光夫    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   評議員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Nov/CCN3 regulates long-term repopulating activity of murine hematopoietic stem cells via integrin αvβ3.
掲載誌名	正式名：International journal of hematology 略　 称：Int J Hematol ISSNコード：(1865-3774)0925-5710(Linking)
掲載区分	国外
巻・号・頁	99(4),pp.393-406
著者・共著者	ISHIHARA Jun†, UMEMOTO Terumasa, YAMATO Masayuki*, SHIRATSUCHI Yoshiko, TAKAKI Satoshi, PETRICH Brian G., NAKAUCHI Hiromitsu, ETO Koji, KITAMURA Toshio, OKANO Teruo
担当区分	最終著者
発行年月	2014/04
概要	Throughout life, hematopoietic stem cells (HSCs) sustain the blood cell supply through their capacities for self-renewal and multilineage differentiation. These processes are regulated within a specialized microenvironment termed the 'niche'. Here, we show a novel mechanism for regulating HSC function that is mediated by nephroblastoma overexpressed (Nov/CCN3), a matricellular protein member of the CCN family. We found that Nov contributes to the maintenance of long-term repopulating (LTR) activity through association with integrin αvβ3 on HSCs. The resultant β3 integrin outside-in signaling is dependent on thrombopoietin (TPO), a crucial cytokine involved in HSC maintenance. TPO was required for Nov binding to integrin αvβ3, and stimulated Nov expression in HSCs. However, in the presence of IFNγ, a cytokine known to impair HSC function, not only was TPO-induced expression of Nov suppressed, but the LTR activity was conversely impaired by TPO-mediated ligation of integrin αvβ3 with exogenous ligands, including Nov, as well. Thus, Nov/integrin αvβ3-mediated maintenance of HSCs appears to be modulated by simultaneous stimulation by other cytokines. Our finding suggests that this system contributes to the regulation of HSCs within the bone marrow niche.
DOI	10.1007/s12185-014-1534-x
PMID	24563081