Wang Yongliang, Rouabhia Mahmoud, Zhang Ze
Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, QC, Canada; Axe Médecine régénératrice, Centre de Recherche du CHU de Québec, Département de Chirurgie, Faculté de Médecine, Université Laval, QC, Canada.
Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, QC, Canada.
Biochim Biophys Acta. 2016 Jul;1860(7):1551-9. doi: 10.1016/j.bbagen.2016.03.023. Epub 2016 Apr 1.
Dermal fibroblasts activated by conductive polymer-mediated electrical stimulation (ES) have shown myofibroblast characteristics that favor wound healing. However, the signaling pathway related to this phenotype switch remains unclear, and the in vivo survival of the electrically activated cells has never been studied.
Primary human skin fibroblasts were exposed to pulsed-ES mediated through polypyrrole (PPy) coated fabrics. The expression of α-smooth muscle actin (α-SMA) and the signaling pathways were investigated by ELISA, Western blot and specific inhibition test, and immunocytochemistry staining as well as qRT-PCR analysis. In vivo implantation was performed in a mouse model to clarify the cell fate or contractile phenotype maintenance following ES stimulation.
We demonstrated the upregulation of TGFβ1 and phosph-ERK, and the NF-κB nuclear enrichment in the ES-activated cells. The ES-activated fibroblasts retained high level of α-smooth muscle actin expression even after prolonged subculture. Subcutaneous implantation for 15 days revealed more human myofibroblasts in the experimental groups.
These findings demonstrate for the first time the involvement of the TGFβ1/ERK/NF-κB signaling pathway in ES-activated fibroblasts. The ES induced phenotype switch proves stable in subculture and in animal, pointing potential application in wound healing.
Reveal of how ES activates cells and the implication of ES activated cells in wound healing.
导电聚合物介导的电刺激（ES）激活的真皮成纤维细胞已表现出有利于伤口愈合的肌成纤维细胞特征。然而，与这种表型转换相关的信号通路仍不清楚，并且电激活细胞在体内的存活情况从未被研究过。
将原代人皮肤成纤维细胞暴露于通过聚吡咯（PPy）涂层织物介导的脉冲ES中。通过酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法和特异性抑制试验、免疫细胞化学染色以及定量逆转录聚合酶链反应（qRT-PCR）分析来研究α平滑肌肌动蛋白（α-SMA）的表达和信号通路。在小鼠模型中进行体内植入，以阐明ES刺激后细胞命运或收缩表型的维持情况。
我们证明了ES激活的细胞中转化生长因子β1（TGFβ1）和磷酸化细胞外调节蛋白激酶（phosph-ERK）上调，以及核因子κB（NF-κB）核富集。即使在长期传代培养后，ES激活的成纤维细胞仍保持高水平的α平滑肌肌动蛋白表达。皮下植入15天显示实验组中有更多的人肌成纤维细胞。
这些发现首次证明了TGFβ1/ERK/NF-κB信号通路参与ES激活的成纤维细胞。ES诱导的表型转换在传代培养和动物体内均证明是稳定的，表明其在伤口愈合中有潜在应用。
揭示ES如何激活细胞以及ES激活的细胞在伤口愈合中的意义。
