Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions.
J Immunol
; 183(4): 2495-505, 2009 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-19625652
ABSTRACT
Hematopoietic stem cells (HSCs) are maintained in a quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signals. The mechanisms regulating the quiescence and mobilization of HSCs, however, remain unclear. In this study, we report that the expression of thioredoxin-interacting protein (TXNIP) is decreased during HSC activation. In Txnip(-/-) mice, the long-term reconstituting HSC population is decreased and exhausted, and its capacity to repopulate is rapidly lost. These effects are associated with hyperactive Wnt signaling, an active cell cycle, and reduced p21 expression under conditions of stress. TXNIP deficiency reduced the CXCL12- and osteopontin-mediated interaction between HSCs and the bone marrow, and impaired homing and retention in the osteoblastic niche, resulting in mobilized HSCs. Therefore, we propose that TXNIP is essential for maintaining HSC quiescence and the interaction between HSCs and the BM niche.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Estrés Fisiológico
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Tiorredoxinas
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Células Madre Hematopoyéticas
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Proteínas Portadoras
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Movimiento Celular
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Fase de Descanso del Ciclo Celular
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2009
Tipo del documento:
Article