Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy

Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy
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DOI:
10.1152/ajpcell.00496.2006
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发表时间:
2007-04-01
影响因子:
5.5
通讯作者:
Alway, Stephen E.
Alway, Stephen E.
中科院分区:
生物学2区
文献类型:
--
作者:
Pistilli, Emidio E.;Siu, Parco M.;Alway, Stephen E.

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白细胞介素-15(IL-15)mRNA在骨骼肌中组成性表达。尽管IL-15在体外具有肥大和抗凋亡作用,但其在体内骨骼肌细胞中的作用尚不清楚。本研究的目的是确定骨骼肌老化和卸载,两种已知促进肌肉萎缩的条件,是否会改变骨骼肌中的基础IL-15表达。我们假设,IL-15 mRNA的表达将增加作为衰老和肌肉卸载的结果,肌肉将表达功能性三聚体IL-15受体(IL-15 R)的mRNA。本研究采用了两种去负荷模型:大鼠后肢悬吊(HS)和鹌鹑翅膀去负荷。老年大鼠足底肌和比目鱼肌的绝对肌肉湿重显著低于年轻成年大鼠。尽管14天的HS导致年轻成年动物的跖肌和比目鱼肌的肌肉质量减少,但在老年动物的肌肉中未观察到这种效果。在大鼠比目鱼肌和跖肌中观察到IL-15 mRNA的显著老化时间卸载相互作用。来自老年鹌鹑的Patagialis(PAT)肌肉在卸载7天和14天后分别保留了显著的12%和6%的牵张诱导的肥大。年轻鹌鹑的PAT肌肉保留15%的肥大在7天的卸载,但回归到控制水平后14天的卸载。年龄的主要影响,观察到IL-15 mRNA的表达在PAT肌肉在14天的过载,7天的卸载,和14天的卸载。骨骼肌也表达由IL-15 R α、IL-2/15 R β和γ c组成的功能性IL-15 R的mRNA。基于这些数据,我们推测IL- 15 mRNA在萎缩刺激反应中的增加可能是试图抵消老年动物骨骼肌中的肌肉质量损失。需要进一步研究以确定IL- 15/ IL-15 R系统对抗肌肉萎缩的重要性。
Interleukin-15 ( IL-15) mRNA is constitutively expressed in skeletal muscle. Although IL-15 has proposed hypertrophic and anti-apoptotic roles in vitro, its role in skeletal muscle cells in vivo is less clear. The purpose of this study was to determine if skeletal muscle aging and unloading, two conditions known to promote muscle atrophy, would alter basal IL-15 expression in skeletal muscle. We hypothesized that IL-15 mRNA expression would increase as a result of both aging and muscle unloading and that muscle would express the mRNA for a functional trimeric IL-15 receptor ( IL-15R). Two models of unloading were used in this study: hindlimb suspension ( HS) in rats and wing unloading in quail. The absolute muscle wet weight of plantaris and soleus muscles from aged rats was significantly less when compared with muscles from young adult rats. Although 14 days of HS resulted in reduced muscle mass of plantaris and soleus muscles from young adult animals, this effect was not observed in muscles from aged animals. A significant aging times unloading interaction was observed for IL-15 mRNA in both rat soleus and plantaris muscles. Patagialis ( PAT) muscles from aged quail retained a significant 12 and 6% of stretch- induced hypertrophy after 7 and 14 days of unloading, respectively. PAT muscles from young quail retained 15% hypertrophy at 7 days of unloading but regressed to control levels following 14 days of unloading. A main effect of age was observed on IL-15 mRNA expression in PAT muscles at 14 days of overload, 7 days of unloading, and 14 days of unloading. Skeletal muscle also expressed the mRNAs for a functional IL- 15R composed of IL- 15R alpha, IL-2/ 15R-beta, and -gamma c. Based on these data, we speculate that increases in IL- 15 mRNA in response to atrophic stimuli may be an attempt to counteract muscle mass loss in skeletal muscles of old animals. Additional research is warranted to determine the importance of the IL- 15/ IL- 15R system to counter muscle wasting.