Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan.
Gut. 2013 Jun;62(6):882-9. doi: 10.1136/gutjnl-2011-300776. Epub 2012 Jul 31.
Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis.
To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments.
A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells.
These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.
多项流行病学研究表明，规律运动可预防结肠癌的发生，但其潜在机制尚不清楚。肌因子是骨骼肌分泌的蛋白，可促进代谢改善和器官的抗炎作用，是运动带来健康获益的部分原因。本研究旨在鉴定新的肌因子，以预防结肠癌的发生。
为了鉴定新的分泌性肌肉来源蛋白，我们使用 DNA 微阵列比较了久坐和运动的年轻和年老小鼠的肌肉组织转录组。在进行单次运动的小鼠和人中测量了循环分泌蛋白酸性富含半胱氨酸（SPARC）的水平。使用 SPARC 基因敲除小鼠研究了 SPARC 对结肠癌发生的影响。在培养实验中研究了 SPARC 的分泌和功能。
单次运动增加了小鼠和人中骨骼肌中 SPARC 的表达和分泌。此外，在氧化偶氮甲烷诱导的结肠癌小鼠模型中，规律的低强度运动可显著减少野生型小鼠而非 SPARC 基因敲除小鼠中异常隐窝病灶的形成。此外，规律运动可增强结肠黏膜细胞的凋亡，并增加野生型小鼠中 caspase-3 和 caspase-8 的裂解形式，但 SPARC 基因敲除小鼠中则没有。培养实验表明，循环拉伸可诱导肌细胞分泌 SPARC，并通过增加结肠癌细胞的凋亡来抑制增殖。
这些发现表明，运动可刺激肌肉组织分泌 SPARC，而 SPARC 可通过增加凋亡来抑制结肠癌的发生。
