18α-Glycyrrhetinic Acid Induces Phenotypic Changes of Skeletal Muscle Cells to Enter Adipogenesis
18α-Glycyrrhetinic Acid Induces Phenotypic Changes of Skeletal Muscle Cells to Enter Adipogenesis
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DOI：
10.1159/000110438
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发表时间：
2007-10
影响因子：
--
通讯作者：
K. Yamanouchi;E. Yada;N. Ishiguro;M. Nishihara
中科院分区：
文献类型：
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作者：
K. Yamanouchi;E. Yada;N. Ishiguro;M. Nishihara
连接蛋白的重要性与细胞的增殖和分化有关。在骨骼肌细胞中，连接蛋白43（Cx43）已被确定为主要的连接蛋白，并且已显示由连接蛋白介导的缝隙连接通讯是骨骼肌细胞肌原性分化所需的。此外，连接蛋白功能的抑制已显示诱导成骨细胞转分化为脂肪细胞表型。在本研究中，我们研究了连接蛋白功能的抑制是否可以诱导骨骼肌细胞的表型变化。用连接蛋白功能抑制剂18α-大黄酸（AGRA）处理骨骼肌细胞，导致MyoD阳性细胞数量减少，肌管形成完全抑制，同时C/EBPα阳性细胞数量增加。AGRA处理的细胞在成脂分化培养基中培养可以产生同时表达PPARγ和C/EBPα的成熟脂肪细胞。在成脂分化过程中AGRA的存在并不抑制骨骼肌细胞的成脂。AGRA处理不影响骨骼肌细胞中Cx43的表达，但降低其磷酸化。这些结果表明，连接蛋白功能的抑制诱导骨骼肌细胞进入脂肪形成的表型变化。
The importance of connexins is implicated in proliferation and differentiation of cells. In skeletal muscle cells, connexin43 (Cx43) has been identified as the major connexin, and gap-junctional communication mediated by connexins has been shown to be required for their myogenic differentiation. In addition, inhibition of connexin function has been shown to induce transdifferentiation of osteoblasts to an adipocytic phenotype. In the present study, we examined whether the inhibition of connexin function could induce phenotypic changes in skeletal muscle cells. Treatment of skeletal muscle cells with an inhibitor of connexin function, 18α-glycyrrhetinic acid (AGRA), resulted in a reduction in the number of MyoD-positive cells and complete inhibition of myotube formation, concomitantly with an increase in the number of C/EBPα-positive cells. AGRA-treated cells cultured in adipogenic differentiation medium could give rise to mature adipocytes that express both PPARγ and C/EBPα. The presence of AGRA during adipogenic differentiation did not inhibit adipogenesis of skeletal muscle cells. AGRA treatment did not affect Cx43 expression in skeletal muscle cells but reduced its phosphorylation. These results indicate that inhibition of connexin function induces phenotypic changes of skeletal muscle cells to enter adipogenesis.