Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling pathways
Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling pathways
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DOI：
10.1074/jbc.m606089200
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发表时间：
2006-12-08
影响因子：
4.8
通讯作者：
Miyajima, Atsushi
中科院分区：
文献类型：
--
作者：
Miyaoka, Yuichiro;Tanaka, Minoru;Miyajima, Atsushi
脂肪细胞在能量平衡中起着关键作用，并且已经显示出几种细胞因子调节脂肪形成。虽然以前报道过白细胞介素（IL）-6家族的细胞因子参与脂肪形成，但该家族在脂肪形成中的作用及其作用机制尚未完全了解。在这里，我们表明，在IL-6家族中，制瘤素M（OSM）最强烈地抑制3 T3-L1细胞和小鼠胚胎成纤维细胞（MEFs）的脂肪形成。我们还表明，OSM抑制脂肪形成通过Ras/细胞外信号调节激酶（ERK）和信号转导和转录激活因子（STAT）5信号通路。此外，OSM抑制分化的早期阶段，而不影响整个脂肪形成过程中的细胞增殖，包括有丝分裂克隆扩增。已知CCAAT/增强子结合蛋白（C/EBP）α、C/EBP β和过氧化物酶体增殖物激活受体（PPAR）γ是脂肪生成所必需的。OSM几乎完全抑制C/EBP α和PPAR γ的表达。相反，OSM对C/EBP β的mRNA和蛋白水平均无影响。在曲格列酮存在下，C/EBP β的强制表达诱导分化，OSM抑制这种C/EBP β诱导的分化。总而言之，我们的结果表明OSM可能通过调节C/EBP β活性来抑制Ras/ERK和STAT 5信号通路中脂肪细胞终末分化的开始。
Adipocytes play a key role in energy homeostasis and several cytokines have been shown to regulate adipogenesis. While the interleukin (IL)-6 family of cytokines was previously reported to be involved in adipogenesis, roles of this family in adipogenesis and their mechanisms of action are not fully understood. Here we show that among the IL-6 family, oncostatin M (OSM) most strongly inhibits adipogenesis of 3T3-L1 cells and mouse embryonic fibroblasts (MEFs). We also demonstrate that OSM inhibits adipogenesis through the Ras/extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT) 5 signaling pathways. In addition, OSM inhibits the early phase of the differentiation without affecting cell proliferation throughout adipogenesis including mitotic clonal expansion. CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, and peroxisome proliferator-activated receptor (PPAR) gamma are known to be required for adipogenesis. Expression of C/EBP alpha, and PPAR gamma was almost completely abrogated by OSM. In contrast, neither the mRNA nor protein level of C/EBP beta was affected by OSM. Forced expression of C/EBP beta induced differentiation in the presence of troglitazone, and OSM inhibited this C/EBP beta-induced differentiation. Taken together, our results indicate that OSM inhibits the onset of terminal differentiation of adipocytes through the Ras/ERK and STAT5 signaling pathways by possibly regulating C/EBP beta activity.