TLR4-mediated activation of the ERK pathway following UVA irradiation contributes to increased cytokine and MMP expression in senescent human dermal fibroblasts.
TLR4-mediated activation of the ERK pathway following UVA irradiation contributes to increased cytokine and MMP expression in senescent human dermal fibroblasts.
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DOI：
10.1371/journal.pone.0202323
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Shin OS
中科院分区：
文献类型：
--
作者：
Seo SW;Park SK;Oh SJ;Shin OS
暴露于紫外线（UV）辐射是导致过早老化（光老化）和皮肤癌的主要因素。细胞衰老的体外模型已被证明对于研究导致老化皮肤细胞生长停滞的损伤的缓慢和进行性积累非常有用。在这项研究中，我们比较了UVA诱导的非衰老（NS）与衰老（S）人皮肤成纤维细胞（HDF）的细胞反应。用单剂量的UVA（7.5J/cm 2）照射HDF，并进行QuantSeq 3' mRNA测序以评估差异基因表达。NS和S HDFs表达相似数量的差异表达基因，尽管两组之间差异表达的基因不同。与NS HDFs相比，S HDFs中检测到基质金属蛋白酶（MMPs）和Toll样受体（TLR）途径基因（如TLR 4，MyD 88和CXCL-8）的表达更高，UVA暴露导致胶原基因（如COL 8A 2和COL 5A 3）下调。与基因表达谱一致，S HDFs中观察到的IL-6和IL-8分泌增强，与NS HDFs相比，对UVA的反应。此外，我们发现TLR 4介导的ERK途径是负责UVA介导的线粒体功能障碍，以及增加分泌MMP-1和IL-8在S HDFs。总之，我们的研究结果表明UVA诱导的NS和S HDFs之间的细胞反应的共同和不同的分子模式，并建议TLR 4/ERK途径作为候选目标，以减少衰老表型。
Exposure to ultraviolet (UV) radiation is a major contributing factor to premature aging (photoaging) and skin cancer. In vitro models of cellular senescence have proven to be very useful for the study of slow and progressive accumulation of damage resulting in the growth arrest of aging skin cells. In this study, we compared UVA-induced cellular responses in non-senescent (NS) vs. senescent (S) human dermal fibroblasts (HDFs). HDFs were irradiated with a single dose of UVA (7.5 J/cm2) and QuantSeq 3' mRNA sequencing was performed to assess differential gene expression. Both NS and S HDFs expressed similar numbers of differentially expressed genes, although distinct sets of genes were differentially expressed between the two groups. Higher expression of matrix metalloproteinases (MMPs) and Toll-like receptor (TLR) pathway genes, such as TLR4, MyD88, and CXCL-8, was detected in S HDFs as compared with NS HDFs, and UVA exposure led to a downregulation of collagen genes, such as COL8A2 and COL5A3. Consistent with gene expression profiling, enhanced IL-6 and IL-8 secretion was observed in S HDFs compared with NS HDFs, in response to UVA. Furthermore, we show that TLR4-mediated ERK pathway is responsible for the UVA-mediated mitochondrial dysfunction as well as increased secretion of MMP-1 and IL-8 in S HDFs. Taken together, our results demonstrate the UVA-induced common and distinct molecular patterns of cellular responses between NS and S HDFs and suggest TLR4/ERK pathways as candidate targets to reduce senescent phenotypes.
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DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
3.2
作者：
Harberts E;Fishelevich R;Liu J;Atamas SP;Gaspari AA
通讯作者：
Gaspari AA
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
3.6
作者：
Park, Seul-Ki;Shin, Ok Sarah
通讯作者：
Shin, Ok Sarah
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