Insulin-Like Growth Factor-1 Promotes Wound Healing in Estrogen-Deprived Mice: New Insights into Cutaneous IGF-1R/ERα Cross Talk
Insulin-Like Growth Factor-1 Promotes Wound Healing in Estrogen-Deprived Mice: New Insights into Cutaneous IGF-1R/ERα Cross Talk
复制标题
DOI：
10.1038/jid.2012.228
复制
发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Hardman, Matthew J.
中科院分区：
文献类型：
--
作者：
Emmerson, Elaine;Campbell, Laura;Hardman, Matthew J.
虽然可以理解内源性IGF-1参与伤口修复过程，但外源性IGF-1给药对伤口修复的影响在很大程度上仍不清楚。此外，IGF-1受体（IGF-1 R）和雌激素受体（ER）之间的信号联系，已在其他系统中阐明，尚未在皮肤修复的背景下进行探索。在这项研究中，我们表明，局部给药的IGF-1促进伤口修复的雌激素剥夺的动物模型，卵巢切除（OVX）小鼠，主要是通过抑制局部炎症反应和促进上皮再生。使用特定的IGF-1 R和ER拮抗剂在体内，我们发现，IGF-1介导的再上皮化的影响是直接介导的IGF-1 R。相比之下，IGF-1的抗炎作用主要是通过ER，特别是ER α。至关重要的是，在ER α缺失的小鼠中，IGF-1不能促进愈合，局部炎症增加。我们的研究结果说明了皮肤中IGF-1和雌激素之间的复杂相互作用。事实上，IGF-1可以补偿伤口修复中的雌激素缺乏，以及潜在的其他情况，是治疗绝经后病理的重要考虑因素。Journal of Investigative Dermatology（2012）132，2838-2848; doi：10.1038/jid.2012.228; 2012年7月19日在线发表
Although it is understood that endogenous IGF-1 is involved in the wound repair process, the effects of exogenous IGF-1 administration on wound repair remain largely unclear. In addition, the signaling links between IGF-1 receptor (IGF-1R) and estrogen receptors (ERs), which have been elucidated in other systems, have yet to be explored in the context of skin repair. In this study, we show that locally administered IGF-1 promotes wound repair in an estrogen-deprived animal model, the ovariectomized (Ovx) mouse, principally by dampening the local inflammatory response and promoting re-epithelialization. Using specific IGF-1R and ER antagonists in vivo, we reveal that IGF-1-mediated effects on re-epithelialization are directly mediated by IGF-1R. By contrast, the anti-inflammatory effects of IGF-1 are predominantly via the ERs, in particular ER alpha. Crucially, in ER alpha-null mice, IGF-1 fails to promote healing, and local inflammation is increased. Our findings illustrate the complex interactions between IGF-1 and estrogen in skin. The fact that IGF-1 may compensate for estrogen deficiency in wound repair, and potentially other contexts, is an important consideration for the treatment of postmenopausal pathology. Journal of Investigative Dermatology (2012) 132, 2838-2848; doi:10.1038/jid.2012.228; published online 19 July 2012