Upregulation of gene encoding adipogenic transcriptional factors C/EBPα and PPARγ2 in denervated muscle
Upregulation of gene encoding adipogenic transcriptional factors C/EBPα and PPARγ2 in denervated muscle
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DOI：
10.1113/expphysiol.2006.033662
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发表时间：
2006-07-01
影响因子：
2.7
通讯作者：
Wagatsuma, A.
中科院分区：
文献类型：
--
作者：
Wagatsuma, A.
肌肉去神经支配诱导骨骼肌脂肪变性。然而，可能的机制仍有待阐明。为了深入了解这一过程的调控，本研究旨在表征失神经支配肌肉中调节脂肪形成的转录因子和脂肪细胞终末分化标志物的基因表达模式。雌性小鼠手术切除坐骨神经，术后5、10、20、30天切除腓肠肌。油红O染色评价脂肪变性程度为脂质积累。采用免疫组织化学方法检测CCCAT/增强子结合蛋白α (C/EBP α)和过氧化物酶体增殖物激活受体γ 2 （PPAR γ 2）的细胞定位，这两种受体在脂肪细胞分化调控中发挥重要作用。采用实时聚合酶链反应分析mRNA水平。肌肉去神经支配后，大部分肌纤维病理萎缩，腓肠肌浅表区出现脂质积累，提示该模型发生脂肪变性。C/EBP α和PPAR γ 2蛋白在去神经支配肌间质中均有表达，而在正常肌中有少量表达。肌肉去神经后30 d， C/EBP α和PPAR γ 2的表达水平显著上调。反映脂肪酸代谢的脂肪酸结合蛋白4 （fatty acid binding protein 4, FABP4）表达量在肌肉去神经后第5天和第10天略有下降，30天后恢复到对照水平。这些发现表明，肌肉去神经支配诱导的脂肪变性可能通过C/EBP α和PPAR γ 2介导。
Muscle denervation induces fatty degeneration in skeletal muscle. However, the possible mechanism(s) remains to be elucidated. To gain insight into the regulation of this process, this study was designed to characterize the expression pattern of genes encoding transcriptional factors that regulate adipogenesis and the terminal differentiation marker of adipocytes in denervated muscle. Female mice underwent surgery to transect the sciatic nerve, and then the gastrocnemius muscles were harvested 5, 10, 20 or 30 days after surgery. The extent of fatty degeneration was assessed as lipid accumulation by Oil Red O staining. The cellular localization of CCCAT/enhancer-binding protein alpha (C/EBP alpha) and peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2), which play an important role in the regulation of adipocyte differentiation, was assessed by immunohistochemistry. The mRNA levels were analysed using a real-time polymerase chain reaction. After muscle denervation, most muscle fibres atrophied pathologically, and lipid accumulation was observed in the superficial region of the gastrocnemius muscle, suggesting that fatty degeneration occurs in this model. Both C/EBP alpha and PPAR gamma 2 proteins were observed in the interstitial space of denervated muscle but detected in small amounts in normal muscle. The expression levels of C/EBP alpha and PPAR gamma 2 were significantly upregulated 30 days after muscle denervation. The expression levels of fatty acid binding protein 4 (FABP4), which reflects fatty acid metabolism, were decreased slightly at 5 and 10 days and then returned to control levels 30 days after muscle denervation. These findings suggest that muscle denervation-induced fatty degeneration may be mediated through C/EBP alpha and PPAR gamma 2.