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KMID : 0620920170490120007
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Experimental & Molecular Medicine
2017 Volume.49 No. 12 p.7 ~ p.7
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IL-11 promotes the treatment efficacy of hematopoietic stem cell transplant therapy in aplastic anemia model mice through a NF-κB/microRNA-204/thrombopoietin regulatory axis
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Wang Yan
Niu Zhi Yun
Guo Yu Jie
Wang Li Hua
Lin Feng Ru
Zhang Jing Yu
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Abstract
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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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KEYWORD
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Cell biology, Haematopoietic stem cells
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