Prostaglandin F 2 stimulates growth of skeletal muscle cells via an NFATC 2-dependent pathway

Prostaglandin F 2 stimulates growth of skeletal muscle cells via an NFATC 2-dependent pathway
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前列腺素 F 2 通过 NFATC 2 依赖性途径刺激骨骼肌细胞生长

DOI:
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发表时间:
2003
期刊:
影响因子:
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通讯作者:
G. Pavlath
G. Pavlath
中科院分区:
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文献类型:
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作者:
V. Horsley;G. Pavlath

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骨骼肌的生长需要多个步骤来形成大的多核肌细胞。刺激肌肉生长的分子可能对与衰老、损伤或疾病相关的肌肉损失有治疗作用。然而,很少有已知的因素会增加肌肉细胞的大小。我们证明前列腺素f2 (PGF 2)以及两种类似物在体外增加肌肉细胞的大小。肌管大小的增加不是由于PGF - 2增强最初形成肌管的细胞融合,而是由于PGF - 2招募细胞与先前存在的多核细胞融合。这种生长是通过PGF 2受体(FP受体)介导的。由于FP受体可以增加细胞内钙的水平,因此研究了钙调节转录因子活化T细胞核因子(NFAT)在介导PGF 2增强细胞生长中的作用。我们发现NFAT可被PGF 2激活,并且NFATC2亚型是PGF 2诱导的肌肉细胞生长和核增生所必需的,这证明了前列腺素受体激活和NFAT信号传导之间的第一个交集。鉴于PGF - 2在骨骼肌细胞生长中的新作用,这些研究提出了警告,即长期使用抑制PG生成的药物,如非甾体抗炎药,可能对肌肉生长有害。
keletal muscle growth requires multiple steps to form large multinucleated muscle cells. Molecules that stimulate muscle growth may be therapeutic for muscle loss associated with aging, injury, or disease. However, few factors are known to increase muscle cell size. We demonstrate that prostaglandin F 2 (PGF 2 ) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF 2 -enhancing cell fusion that initially forms myotubes, but rather to PGF 2 recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF 2 receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the S involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF 2 -enhanced cell growth was examined. We show that NFAT is activated by PGF 2 , and the isoform NFATC2 is required for PGF 2 -induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF 2 in skeletal muscle cell growth, these studies raise caution that extended use of drugs that inhibit PG production, such as nonsteroidal antiinflammatory drugs, may be deleterious for muscle growth.
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