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- 자료유형
- 학술저널
- 저자정보
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- 2017.1
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Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function.
However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro. Through inhibiting NF-кB activity, miR-204-5p repression was demonstrated to be a downstream effect of IL-11 signaling. miR-204-5p was shown to directly target thrombopoietin (TPO) via sequence-dependent 3′-UTR repression, indicating that this microRNA-dependent pathway could serve an essential role in supporting IL-11 functions in HSCs. Increased TPO expression in HSCs following IL-11 exposure could be mimicked or blocked by inhibiting or overexpressing miR-204-5p, respectively. Consistent with these in vitro findings, IL-11 promoted HSC engraftment in a mouse model of AA, an effect that was attenuated in cells overexpressing miR-204-5p. The reduction in miR-204-5p levels is an integral component of IL-11 signaling that may play an essential role in treating AA.
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참고문헌 (26)
참고문헌 신청
Betel D / 2010 / Com
Bozza M / 2001 / Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells / J Interf Cytok Res 21 : 21 ~ 30
Curti A / 2001 / Interleukin-11 induces Th2 polarization of human CD4(+)T cells / Blood 97 : 2758 ~ 2763
DeZern AE / 2011 / Clinical management of aplastic anemia / Expert Rev Hematol 4 : 221 ~ 230
Du X / 1997 / Interleukin-11: review of molecular, cell biology, and clinical use / Blood 89 : 3897 ~ 3908
Bozza M / 2001 / Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells / J Interf Cytok Res 21 : 21 ~ 30
Curti A / 2001 / Interleukin-11 induces Th2 polarization of human CD4(+)T cells / Blood 97 : 2758 ~ 2763
DeZern AE / 2011 / Clinical management of aplastic anemia / Expert Rev Hematol 4 : 221 ~ 230
Du X / 1997 / Interleukin-11: review of molecular, cell biology, and clinical use / Blood 89 : 3897 ~ 3908
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