MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
J Cell Physiol. 2014 Jan;229(1):108-16. doi: 10.1002/jcp.24425.
Cellular senescence is a growth-arrest program that limits cell proliferation. Low-power laser irradiation (LPLI) has been demonstrated to promote cell proliferation. However, whether LPLI can inhibit cellular senescence remains unknown. In the present study, to investigate the functional role of LPLI against skin aging, we used ultraviolet radiation b (UVB) to induce cell senescence. We first report that LPLI can delay UVB-induced cell senescence. The senescence-associated β-galactosidase (SA-β-Gal) activity and p21 expression, hallmarks of senescent cells, were decreased in the Forkhead box transcription factor FOXM1-dependent manner under treatment with LPLI. The effect of LPLI was further enhanced with an overexpression of FOXM1, and abolished when FOXM1 was knockdown with short hairpin RNA (shRNA). Furthermore, LPLI activated the extracellular regulated protein kinases (ERK) that was upstream of FOXM1. This led to FOXM1 phosphorylation and nuclear translocation. Nuclear translocation enhanced FOXM1 transcriptional activity and promoted its downstream target gene c-Myc expression that could inhibit p21 expression. These findings highlight the protective effects of ERK/FOXM1 pathway against UVB-induced cell senescence, suggesting a potential protecting strategy for treating skin aging by LPLI.
细胞衰老（Cellular senescence）是一种限制细胞增殖的生长停滞程序。低强度激光照射（Low-power laser irradiation，LPLI）已被证明可促进细胞增殖。然而，LPLI 是否能抑制细胞衰老尚不清楚。在本研究中，为了研究 LPLI 对皮肤衰老的功能作用，我们使用紫外线 B（Ultraviolet radiation b，UVB）诱导细胞衰老。我们首次报道 LPLI 可延缓 UVB 诱导的细胞衰老。在 LPLI 处理下，衰老相关的β-半乳糖苷酶（Senescence-associated β-galactosidase，SA-β-Gal）活性和 p21 表达（衰老细胞的标志）呈 FoxM1 依赖性下降。FOXM1 的过表达进一步增强了 LPLI 的作用，而短发夹 RNA（short hairpin RNA，shRNA）敲低 FOXM1 则消除了这种作用。此外，LPLI 激活了 FOXM1 的上游细胞外调节蛋白激酶（Extracellular regulated protein kinases，ERK）。这导致 FOXM1 磷酸化和核转位。核转位增强了 FOXM1 的转录活性，并促进其下游靶基因 c-Myc 的表达，从而抑制 p21 的表达。这些发现强调了 ERK/FOXM1 通路对 UVB 诱导的细胞衰老的保护作用，提示 LPLI 治疗皮肤衰老的一种潜在保护策略。
