UVA influenced the SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in human skin primary fibroblasts.
UVA influenced the SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in human skin primary fibroblasts.
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DOI：
10.1111/jcmm.15610
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Chen HD
中科院分区：
文献类型：
--
作者：
Jiang SB;Lu YS;Liu T;Li LM;Wang HX;Wu Y;Gao XH;Chen HD
SIRT 1和UVA辐射都参与细胞损伤过程，如细胞凋亡、衰老和老化。据报道，microRNAs（miRNAs）与紫外线辐射以及SIRT 1密切相关。在这项研究中，我们研究了SIRT 1，UVA和miRNA在人皮肤原代成纤维细胞中的关系。我们的研究结果表明，UVA改变SIRT 1的蛋白水平在一个时间点依赖性的方式。通过miRNA微阵列、生物信息学分析，我们发现敲低SIRT 1可导致miR-27 a-5 p表达上调，而后者可下调SMAD 2，这些结果均得到了qRT-PCR或Western blot的验证。此外，UVA辐射（5 J/cm 2）、敲低SIRT 1或过表达miR-27 a-5 p导致MMP 1表达增加，COL 1和BCL 2表达减少。我们还发现，在UVA辐射+ Sirtinol（SIRT 1抑制剂）或UVA辐射+ miR-27 a-5 p模拟物的组合下，对MMP 1、COL 1和BCL 2的影响是累加的。SIRT 1激活剂白藜芦醇可以逆转UVA辐射引起的损伤变化。此外，SIRT 1的缺失或miR-27 a-5 p的过表达增加了细胞凋亡并诱导细胞停滞在G2/M期。综上所述，这些结果表明，UVA可以影响皮肤原代成纤维细胞中新的SIRT 1-miR-27 a-5 p-SMAD 2-MMP 1/COL 1/BCL 2轴，并可能为UVA诱导的皮肤损伤提供潜在的治疗靶点。
Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point–dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up‐regulation of miR‐27a‐5p and the latter could down‐regulate SMAD2, and these results were verified by qRT‐PCR or Western blot. Furthermore, UVA radiation (5 J/cm2), knocking down SIRT1 or overexpression of miR‐27a‐5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR‐27a‐5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR‐27a‐5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1‐miR‐27a‐5p‐SMAD2‐MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA‐induced skin damage.
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影响因子：
--
作者：
Guan Y;Rao Z;Chen C
通讯作者：
Chen C
影响因子：
4
作者：
Peng, Jie;Zhou, Yuanfei;Peng, Jian
通讯作者：
Peng, Jian
影响因子：
4.6
作者：
Hadar A;Milanesi E;Walczak M;Puzianowska-Kuźnicka M;Kuźnicki J;Squassina A;Niola P;Chillotti C;Attems J;Gozes I;Gurwitz D
通讯作者：
Gurwitz D
DOI：
10.1038/skinbio.2013.176
发表时间：
2013-07-01
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Gilchrest, Barbara A
通讯作者：
Gilchrest, Barbara A
影响因子：
5.6
作者：
D'Orazio J;Jarrett S;Amaro-Ortiz A;Scott T
通讯作者：
Scott T