Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells by activating ERK
Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells by activating ERK
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DOI：
10.1016/j.bbamcr.2004.11.002
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发表时间：
2005-04-15
影响因子：
5.1
通讯作者：
Jo, SA
中科院分区：
文献类型：
--
作者：
Jo, C;Kim, H;Jo, SA
白血病抑制因子 (LIF) 是一种属于白细胞介素 6 家族的多功能细胞因子，已被证明可以刺激受损骨骼肌的再生。尽管 LIE 已被证明可以刺激肌肉细胞增殖，但其在分化中的确切作用尚不清楚。因此，我们检查了 LIF 对培养的 C2C12 成肌细胞分化的影响。在本研究中，我们使用了细菌中表达的非糖基化 LIF 和感染 Ad-LIF 的 NIH3T3 细胞分泌的糖基化 LIF。通过肌球蛋白重链的表达和肌管形成来测量，非糖基化和糖基化的 LIF 都会阻断成肌细胞的分化。用 LIF 处理成肌细胞会诱导 ERK 磷酸化，并且用特异性 MEK 抑制剂 U0126 预处理和显性失活 (DN)-MEK1 瞬时转染可阻断 LIF 诱导的肌生成抑制作用。相比之下，虽然 LIF 激活 STAT3，但 LIF 诱导的 MCK 转录活性抑制并未通过 AG490（一种特定的 Jak 激酶抑制剂）预处理或 DN-STAT3 瞬时转染而逆转。此外，只有在诱导分化后 12 小时内处理细胞时，LIF 才会表现出对肌生成的抑制作用。综上所述，这些结果表明，LIE 通过激活 ERK 信号通路强烈抑制早期肌原性分化，并且其作用与糖基化无关。 (c) 2004 Elsevier B.V. 保留所有权利。
Leukemia inhibitory factor (LIF) is a multi functional cytokine belonging to the interleukin-6 family and has been shown to stimulate regeneration of injured skeletal muscle. Although LIE has been shown to stimulate muscle cell proliferation, its precise role in differentiation is unclear. Thus, we examined the effect of LIF on the differentiation of cultured C2C12 myoblast cells. In this study, we used both non-glycosylated LIF expressed in bacteria and glycosylated LIF secreted from NIH3T3 cells infected with Ad-LIF. Both nonglycosylated and glycosylated LIF blocked differentiation of myoblasts as measured by expression of myosin heavy chain and myotube formation. Treatment of myoblasts with LIF induced phosphorylation of ERK, and the LIF-induced inhibitory effect on myogenesis was blocked by pretreatment with U0126, a specific MEK inhibitor, and transient transfection with dominant negative (DN)-MEK1. In contrast, although LIF activated STAT3, the LIF-induced repression of the MCK transcriptional activity was not reversed by pretreatment with AG490, a specific Jak kinase inhibitor or transient transfection with DN-STAT3. Additionally, LIF exhibited its inhibitory effect on myogenesis only when cells were treated at earlier than 12 h after inducing differentiation. Taken together, these results suggest that LIE strongly inhibited early myogenic differentiation though activation of the ERK signaling pathway and its effect is irrespective of glycosylation. (c) 2004 Elsevier B.V. All rights reserved.