ヤマト マサユキ   YAMATO Masayuki
  大和 雅之
   所属   研究施設 研究施設
   職種   教授
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),393-406頁
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
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