Oguri Gaku, Ikegami Ryo, Ugawa Haruka, Katoh Manami, Obi Syotaro, Sakuma Masashi, Takeda Norihiko, Kano Yutaka, Toyoda Shigeru, Nakajima Toshiaki
Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, JPN.
Department of Information Science and Technology, The University of Electro-Communications, Tokyo, JPN.
Cureus. 2024 Sep 9;16(9):e68974. doi: 10.7759/cureus.68974. eCollection 2024 Sep.
Skeletal muscle atrophy is frequently caused by the disuse of muscles. It impacts quality of life, especially in aging populations and those with chronic diseases. Understanding the molecular mechanisms underlying muscle atrophy is crucial for developing effective therapies.
To investigate the roles of vascular endothelial growth factor (VEGF) and various microRNAs (miRNAs) in muscle atrophy using a mouse model of denervation (DEN)-induced disuse, and to elucidate their interactions and regulatory functions through comprehensive network analysis.
The right sciatic nerve of C57BL/6J mice (n=6) was excised to simulate DEN, with the left serving as a sham surgery control (Sham). Following a two-week period, wet muscle weight was measured. Total RNA was extracted from the tibialis anterior muscle for microarray analysis. Significant expression changes were analyzed via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and miRNet for miRNAs.
Denervated limbs showed a significant reduction in muscle weight. Over 1,000 genes displayed increased expression, while 527 showed reductions to less than half of control levels. VEGF, along with specific miRNAs such as miR-106a-5p, miR-mir20a-5p, mir93-5p and mir17-5p, occupied central regulatory nodes within the gene network. Functional analysis revealed that these molecules are involved in key biological processes including regulation of cell migration, vasculature development, and regulation of endothelial cell proliferation. The increased miRNAs were subjected to further network analysis that revealed significant regulatory interactions with target mRNAs.
VEGF and miRNAs play crucial roles in the progression of skeletal muscle atrophy, offering potential targets for therapeutic interventions aimed at reducing atrophy and enhancing muscle regeneration.
骨骼肌萎缩常由肌肉废用引起。它影响生活质量，尤其在老年人群和患有慢性疾病的人群中。了解肌肉萎缩的分子机制对于开发有效的治疗方法至关重要。
利用去神经支配（DEN）诱导的废用小鼠模型，研究血管内皮生长因子（VEGF）和各种微小RNA（miRNA）在肌肉萎缩中的作用，并通过综合网络分析阐明它们的相互作用和调节功能。
切除C57BL/6J小鼠（n = 6）的右侧坐骨神经以模拟DEN，左侧作为假手术对照（Sham）。两周后，测量湿肌肉重量。从胫前肌提取总RNA进行微阵列分析。通过京都基因与基因组百科全书（KEGG）通路分析和miRNet对miRNA进行显著表达变化分析。
去神经支配的肢体肌肉重量显著降低。超过1000个基因表达增加，而527个基因表达降至对照水平的一半以下。VEGF以及特定的miRNA，如miR-106a-5p、miR-mir20a-5p、mir93-5p和mir17-5p，在基因网络中占据中心调节节点。功能分析表明，这些分子参与关键的生物学过程，包括细胞迁移调节、血管发育和内皮细胞增殖调节。对增加的miRNA进行进一步的网络分析，发现它们与靶mRNA存在显著的调节相互作用。
VEGF和miRNA在骨骼肌萎缩的进展中起关键作用，为旨在减少萎缩和促进肌肉再生的治疗干预提供了潜在靶点。
