The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms
The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms
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DOI：
10.1152/ajpcell.00518.2005
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发表时间：
2006-06-01
影响因子：
5.5
通讯作者：
Pavlath, GK
中科院分区：
文献类型：
--
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
肌肉质量的损失发生在疾病、损伤、衰老和不活动的情况下。正常肌肉质量的恢复取决于肌纤维的生长，其调控尚不完全清楚。环氧合酶（考克斯）-2是催化合成类胡萝卜素的考克斯的两种异构体之一，类胡萝卜素是调节多种生理和病理生理过程的旁分泌激素。以前，我们证明了考克斯-2途径调节肌肉再生过程中肌纤维生长的早期阶段。然而，考克斯-2途径是否在成人肌纤维生长中起着共同的作用，或者在肌肉再生过程中起着特殊的作用还不清楚。因此，我们研究了考克斯-2在小鼠肌萎缩后肌纤维生长过程中的作用。通过后肢悬吊（HS）2周诱导肌肉萎缩，随后是再负荷期，在此期间用考克斯-2选择性抑制剂SC-236（6 mg（.）kg（-1）（.）天（-1））或媒介物。考克斯-2蛋白的表达和SC-236衰减肌纤维生长过程中的比目鱼肌和跖肌重新加载。比目鱼肌中肌纤维生长减弱与肌纤维添加减少和炎症减少有关，而这些过程都不介导SC-236对跖肌生长的影响。此外，考克斯-2（-/-）卫星细胞在体外表现出受损的活化/增殖，表明考克斯-2直接调节肌细胞活性。总之，这些数据表明，考克斯-2途径通过多种机制在各种类型的肌肉生长过程中起着共同的调节作用。
Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg (.) kg(-1) (.) day(-1)) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2(-/-) satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.