Rosiglitazone ameliorates senescence-like phenotypes in a cellular photoaging model
Rosiglitazone ameliorates senescence-like phenotypes in a cellular photoaging model
复制标题
DOI：
10.1016/j.jdermsci.2015.01.007
复制
发表时间：
2015-03-01
影响因子：
4.6
通讯作者：
Liu, Tianyi
中科院分区：
文献类型：
--
作者：
Chen, Liang;Bi, Bo;Liu, Tianyi
背景资料：罗格列酮（RO）是第二代噻唑烷二酮，主要用于治疗非胰岛素依赖型糖尿病，已发现是过氧化物酶体增殖物激活受体-γ（PPAR-gamma）的高亲和力配体。几项研究表明，PPAR-gamma还参与调节与体内衰老过程以及体外细胞衰老相关的氧化应激和慢性炎症。我们试图研究RO预处理是否会抵消光老化过程中使用一个完善的细胞photoagedingmodel.Methods：小鼠皮肤成纤维细胞（MDFs）培养在RO的存在或不存在48小时，然后暴露于重复UVB照射。评估衰老表型，包括细胞活力、衰老相关的β-半乳糖苷酶从SA-β-gal的表达、细胞形态、活性氧的产生、细胞周期、细胞外基质（ECM）的产生和降解等方面进行探讨，并探讨其可能的作用机制。用RO（40 μ M）预处理显著降低了染色强度和SA-β-gal-与UVB组相比，UVB组的细胞形态较长，且呈阳性细胞。RO预处理的细胞也表现出减少UVB诱导的I型胶原降解的MMPs表达下降。此外，我们观察到反作用的细胞周期停滞和抑制UVB诱导的p53和p21在RO的存在下。我们进一步证实了一个显着减少ROS积累伴随着增加过氧化氢酶RO group.Conclusions：RO，一个有效的PPAR-gamma激活剂，抵消衰老样表型，包括长期生长停滞，扁平形态，降解ECM和SA-β-gal阳性染色的MDFs通过抑制基质金属蛋白酶的表达和增加过氧化氢酶的合成时，给予反复UVB照射。RO的新应用可能导致创新和有效的抗光老化疗法。(C)2015年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Rosiglitazone (RO), a second-generation thiazolidinedione used mainly in the treatment of non-insulin-dependent diabetes mellitus, has been discovered to be a high-affinity ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Several studies have revealed that PPAR-gamma is also involved in the regulation of oxidative stress and chronic inflammation associated with aging process in vivo as well as with cellular senescence in vitro. We sought to investigate whether RO pretreatment will counteract the photoaging process using a well-established cellular photoaging model.Methods: Murine dermal fibroblasts (MDFs) were cultured in the absence or presence of RO for 48 h, followed by exposure to repeated UVB irradiation. The senescent phenotypes were evaluated including cell viability, senescence-associated beta-galactosidase (SA-beta-gal) expression, cell morphology, ROS generation, cell cycle, production and degradation of extracellular matrix (ECM), and the potential mechanisms were discussed.Results: Pretreatment with RO (40 mu M) significantly decreased the staining intensity and the percentage of SA-beta-gal-positive cells and reserved the elongated cell shape compared with UVB group. The cells pretreated with RO also showed decreased UVB-induced degradation of type I collagen by decreasing MMPs expressions. In addition, we observed counteraction of cell-cycle arrest and repression of UVB-induced p53 and p21 in the presence of RO. We further confirmed a significant decrease in ROS accumulation accompanied by an increase in catalase in RO group.Conclusions: RO, a potent PPAR-gamma activator, counteracts senescence-like phenotypes, including long-term growth arrest, flattened morphology, degradation of ECM and SA-beta-gal-positive staining in MDFs by inhibiting the expression of MMPs and increasing the synthesis of catalase when administered to repeated UVB irradiation. The novel application of RO may lead to innovative and effective anti-photoaging therapies. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.