Biological responses of three-dimensional cultured fibroblasts by sustained compressive loading include apoptosis and survival activity.
Biological responses of three-dimensional cultured fibroblasts by sustained compressive loading include apoptosis and survival activity.
复制标题
DOI：
10.1371/journal.pone.0104676
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sanada H
中科院分区：
文献类型：
--
作者：
Kanazawa T;Nakagami G;Minematsu T;Yamane T;Huang L;Mugita Y;Noguchi H;Mori T;Sanada H
压力性溃疡的特征是慢性性，这导致由于压力而延迟的伤口愈合。早期干预，以防止延迟愈合，由于压力需要一个预测的方法。然而，没有研究报道由于压力而延迟愈合的预测。因此，本研究着重于基于生物反应的分子标记物，以建立一种评估技术来预测由于压力导致的延迟愈合。我们测试了这样的假设，即施加到三维培养的成纤维细胞的持续压缩负荷导致热休克蛋白（HSP）、CD 44、透明质酸合成酶2（HAS 2）和环氧合酶2（COX 2）的上调，以及通过破坏粘附的凋亡。首先，持续的压缩负荷施加到成纤维细胞接种的胶原海绵。在此之后，收集胶原海绵样品和培养上清液用于细胞凋亡和增殖测定、基因表达分析、免疫细胞化学和定量由mRNA和蛋白质水平上调诱导的分泌物质。与对照组相比，压缩样品显示以时间和负荷依赖性方式诱导细胞凋亡;黏着斑蛋白和应力纤维缺乏; HSP 90 α、CD 44、HAS 2和COX 2表达上调; HSP 90 α、透明质酸（HA）和前列腺素E2（PGE 2）浓度增加。此外，与对照组相比，压缩样品中抗凋亡Bcl 2的基因表达显著增加。这些结果表明，压缩负荷不仅诱导细胞凋亡，但也生存活动。这些观察结果支持HSP 90 α、HA和PGE 2可能是预测压力所致伤口延迟愈合的潜在分子标志物。
Pressure ulcers are characterized by chronicity, which results in delayed wound healing due to pressure. Early intervention for preventing delayed healing due to pressure requires a prediction method. However, no study has reported the prediction of delayed healing due to pressure. Therefore, this study focused on biological response-based molecular markers for the establishment of an assessment technology to predict delayed healing due to pressure. We tested the hypothesis that sustained compressive loading applied to three dimensional cultured fibroblasts leads to upregulation of heat shock proteins (HSPs), CD44, hyaluronan synthase 2 (HAS2), and cyclooxygenase 2 (COX2) along with apoptosis via disruption of adhesion. First, sustained compressive loading was applied to fibroblast-seeded collagen sponges. Following this, collagen sponge samples and culture supernatants were collected for apoptosis and proliferation assays, gene expression analysis, immunocytochemistry, and quantification of secreted substances induced by upregulation of mRNA and protein level. Compared to the control, the compressed samples demonstrated that apoptosis was induced in a time- and load- dependent manner; vinculin and stress fiber were scarce; HSP90α, CD44, HAS2, and COX2 expression was upregulated; and the concentrations of HSP90α, hyaluronan (HA), and prostaglandin E2 (PGE2) were increased. In addition, the gene expression of antiapoptotic Bcl2 was significantly increased in the compressed samples compared to the control. These results suggest that compressive loading induces not only apoptosis but also survival activity. These observations support that HSP90α, HA, and, PGE2 could be potential molecular markers for prediction of delayed wound healing due to pressure.
登录
查看更多内容
影响因子：
3.8
作者：
Harper LJ;Costea DE;Gammon L;Fazil B;Biddle A;Mackenzie IC
通讯作者：
Mackenzie IC
影响因子：
7.5
作者：
Gilmore, Andrew P.;Owens, Thomas W.;Lindsay, Jennefer
通讯作者：
Lindsay, Jennefer
影响因子：
4.9
作者：
Falcone, SJ;Palmeri, DM;Berg, RA
通讯作者：
Berg, RA
影响因子：
11.1
作者：
Gerdin, B;Hallgren, R
通讯作者：
Hallgren, R
影响因子：
3.5
作者：
de Araujo, R. M. S.;Oba, Y.;Moriyama, K.
通讯作者：
Moriyama, K.