Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway.
Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway.
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前列腺素F2（α）通过NFATC2依赖性途径刺激骨骼肌细胞的生长。
DOI：
10.1083/jcb.200208085
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发表时间：
2003-04-14
期刊：
影响因子：
--
通讯作者：
Pavlath GK
中科院分区：
文献类型：
--
作者：
Horsley V;Pavlath GK
骨骼肌生长需要多个步骤来形成大的多核肌肉细胞。刺激肌肉生长的分子可以治疗与衰老、损伤或疾病相关的肌肉损失。然而，很少有已知的因素增加肌肉细胞的大小。我们证明，前列腺素F2α（PGF2α）以及两种类似物在体外增加肌细胞的大小。这种肌管尺寸的增加不是由于PGF 2 α促进最初形成肌管的细胞融合，而是由于PGF 2 α募集细胞与预先存在的多核细胞的融合。这种生长通过PGF 2 α受体（FP受体）介导。由于FP受体可增加细胞内钙水平，因此检查了钙调节转录因子活化T细胞核因子（NFAT）介导PGF 2 α增强细胞生长的参与情况。我们发现，NFAT被PGF2α激活，并且PGF2α诱导的肌细胞生长和核增生需要亚型NFATC2，这表明前列腺素受体激活和NFAT信号传导之间的第一个交叉点。鉴于PGF2α在骨骼肌细胞生长中的这种新作用，这些研究提出了警告，即长期使用抑制PG产生的药物，如非甾体类药物，可能对肌肉生长有害。
Skeletal 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 F2α (PGF2α) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF2α-enhancing cell fusion that initially forms myotubes, but rather to PGF2α recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF2α receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF2α-enhanced cell growth was examined. We show that NFAT is activated by PGF2α, and the isoform NFATC2 is required for PGF2α-induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF2α 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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DOI：
10.1083/jcb.153.2.329
发表时间：
2001-04-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Horsley V;Friday BB;Matteson S;Kegley KM;Gephart J;Pavlath GK
通讯作者：
Pavlath GK
影响因子：
7.8
作者：
ENTWISTLE, A;CURTIS, DH;ZALIN, RJ
通讯作者：
ZALIN, RJ
影响因子：
4.8
作者：
Kunapuli, P;Lawson, JA;FitzGerald, GA
通讯作者：
FitzGerald, GA
影响因子：
4.8
作者：
Katsuyama, M;Fan, CY;Yabe-Nishimura, C
通讯作者：
Yabe-Nishimura, C
影响因子：
5.3
作者：
Delling, U;Tureckova, J;Molkentin, JD
通讯作者：
Molkentin, JD