Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats.
Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats.
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DOI：
10.1113/expphysiol.2008.046136
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发表时间：
2009-06
影响因子：
2.7
通讯作者：
Lees SJ
中科院分区：
文献类型：
--
作者：
Jump SS;Childs TE;Zwetsloot KA;Booth FW;Lees SJ
在老年骨骼肌中，再生和再生的损伤可以通过肌肉前体细胞（MPC）对环境线索（例如生长因子）的反应性降低来解释。我们假设，受损的反应，成纤维细胞生长因子2（FGF 2）在MPC从老年动物将被解释为受损的FGF 2信号。我们测定了与3月龄大鼠相比，32月龄大鼠的MPC中5-溴-2 ′-脱氧尿苷（BrdU）掺入和细胞数量增加较少。在FGF 2的存在下，我们证明了FGF受体1和2 mRNA存在与年龄相关的差异表达模式。下游信号转导的测量显示，丝裂原活化蛋白激酶/ERK激酶1/2（MEK 1/2）-细胞外信号调节激酶1/2，蛋白激酶C和p38是FGF 2在MPC中驱动的通路。独特的是，蛋白激酶C信号被证明在MPCs中FGF 2刺激的增殖中发挥最大的作用。c-Jun N末端激酶（JNK）信号传导被排除为MPC中FGF 2刺激的增殖途径。抑制JNK对FGF 2信号传导至BrdU掺入没有影响，并且FGF 2处理与p38磷酸化增加相关，p38磷酸化抑制而不是刺激MPC中BrdU掺入。令人惊讶的是，常用的媒介物二甲基亚砜拯救了老年动物MPC的增殖。这些发现为针对老年骨骼肌中MPC增殖的年龄相关损伤的有效治疗策略的发展提供了见解。
In aged skeletal muscle, impairments in regrowth and regeneration may be explained by a decreased responsiveness of muscle precursor cells (MPCs) to environmental cues such as growth factors. We hypothesized that impaired responsiveness to fibroblast growth factor 2 (FGF2) in MPCs from old animals would be explained by impaired FGF2 signalling. We determined that 5-bromo-2′-deoxyuridine (BrdU) incorporation and cell number increase less in MPCs from 32- compared with 3-month-old rats. In the presence of FGF2, we demonstrated that there were age-associated differential expression patterns for FGF receptor 1 and 2 mRNAs. Measurement of downstream signalling revealed that that mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2)–extracellular signal-regulated kinase 1/2, protein kinase C and p38 were FGF2-driven pathways in MPCs. Uniquely, protein kinase C signalling was shown to play the largest role in FGF2-stimulated proliferation in MPCs. c-Jun N-terminal kinase (JNK) signalling was ruled out as an FGF2-stimulated proliferation pathway in MPCs. Inhibition of JNK had no effect on FGF2 signalling to BrdU incorporation, and FGF2 treatment was associated with increased phosphorylation of p38, which inhibits, rather than stimulates, BrdU incorporation in MPCs. Surprisingly, the commonly used vehicle, dimethyl sulphoxide, rescued proliferation in MPCs from old animals. These findings provide insight for the development of effective treatment strategies that target the age-related impairments of MPC proliferation in old skeletal muscle.