Rapamycin Protects Skin Fibroblasts From UVA-Induced Photoaging by Inhibition of p53 and Phosphorylated HSP27.
Rapamycin Protects Skin Fibroblasts From UVA-Induced Photoaging by Inhibition of p53 and Phosphorylated HSP27.
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雷帕霉素通过抑制 p53 和磷酸化 HSP27 保护皮肤成纤维细胞免受 UVA 诱导的光老化
DOI：
10.3389/fcell.2021.633331
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发表时间：
2021
影响因子：
5.5
通讯作者：
Chen AJ
中科院分区：
文献类型：
--
作者：
Bai GL;Wang P;Huang X;Wang ZY;Cao D;Liu C;Liu YY;Li RL;Chen AJ
由紫外线辐射引起的皮肤老化被称为光老化，其特征在于皮肤粗糙和干燥，伴随着真皮胶原蛋白的显著减少。雷帕霉素是一种大环内酯类免疫抑制剂，已被证明在细胞和生物体中表现出“抗衰老”作用，然而，其在皮肤光老化中的作用尚不清楚。在这里，我们研究了雷帕霉素和HSP 27的作用，我们以前已经确定为紫外线诱导的HaCat细胞凋亡和衰老的抑制剂，在UVA诱导的原代人皮肤成纤维细胞（HDF）的光老化模型。衰老相关β-半乳糖苷酶（SA-β-gal）染色的结果显示，雷帕霉素显着降低UVA处理的HDF的衰老。此外，雷帕霉素治疗显着增加细胞自噬水平，降低p53和磷酸化HSP 27的表达，并降低UVA诱导的HDF的遗传毒性和氧化细胞应激水平。HSP 27的敲低导致MMP-1和MMP-3的显著增加以及I型胶原表达的减少。雷帕霉素通过激活经典的TGF-β/Smad信号通路和增加MAPK/AP-1的转录活性来减轻这些作用。总之，这些结果表明，雷帕霉素可能作为一种预防和治疗剂UVA诱导的皮肤光老化。
Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.
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影响因子：
5.6
作者：
Wu Y;Wang W;Peng XM;He Y;Xiong YX;Liang HF;Chu L;Zhang BX;Ding ZY;Chen XP
通讯作者：
Chen XP
影响因子：
5.6
作者：
Pittayapruek P;Meephansan J;Prapapan O;Komine M;Ohtsuki M
通讯作者：
Ohtsuki M
影响因子：
7.8
作者：
Wilkinson JE;Burmeister L;Brooks SV;Chan CC;Friedline S;Harrison DE;Hejtmancik JF;Nadon N;Strong R;Wood LK;Woodward MA;Miller RA
通讯作者：
Miller RA
影响因子：
5.5
作者：
Mrakovcic M;Fröhlich LF
通讯作者：
Fröhlich LF
影响因子：
3.7
作者：
Seo SW;Park SK;Oh SJ;Shin OS
通讯作者：
Shin OS