Activation of the Wnt/-Catenin Pathway by an Inflammatory Microenvironment Affects the Myogenic Differentiation Capacity of Human Laryngeal Mucosa Mesenchymal Stromal Cells
Activation of the Wnt/-Catenin Pathway by an Inflammatory Microenvironment Affects the Myogenic Differentiation Capacity of Human Laryngeal Mucosa Mesenchymal Stromal Cells
复制标题
炎症微环境激活Wnt/-Catenin通路影响人喉粘膜间充质基质细胞的生肌分化能力
DOI：
10.1089/scd.2017.0200
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发表时间：
2018-06-01
影响因子：
4
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Yang, Runqin;Yang, Xiaoshan;Jin, Yan
各种微环境影响间充质基质细胞的多向分化潜能。例如，炎性微环境可抑制喉粘膜间充质基质细胞（LM-MSCs）的成肌分化能力。因此，本研究试图确定调节这些过程的潜在分子机制。我们从喉粘膜组织中分离出一种新的间充质干细胞群LM-MSCs。在存在或不存在白细胞介素-1和肿瘤坏死因子（以模拟炎症微环境）的情况下，在成骨、成脂和成肌分化培养基中培养细胞。Western blot和实时荧光定量PCR检测细胞中活性β-catenin、p-GSK 3和GSK 3的表达。在体内和体外检测LM-MSCs在炎症微环境中的成肌分化以及Dickkopf-1（DKK 1）的调节作用。炎症微环境可抑制LM-MSCs的成骨、成脂和成肌。Wnt/β-catenin信号通路在炎症微环境中的肌生成过程中被激活。DKK 1可逆转炎症微环境中LM-MSCs的成肌分化能力。DKK 1通过调节Wnt/β-catenin信号通路，促进炎症微环境中LM-MSCs向肌源性分化。因此，本研究的结果可能有助于提高LM-MSCs注射治疗声带再生的疗效。
Various microenvironments influence the multiple differentiation potential of mesenchymal stromal cells. For example, inflammatory microenvironment can suppress the myogenic differentiation capability of laryngeal mucosa mesenchymal stromal cells (LM-MSCs). The present study therefore sought to identify the underlying molecular mechanisms regulating these processes. We isolated a novel population of MSCs, LM-MSCs, from the laryngeal mucosa tissues. The cells were cultured in osteogenic, adipogenic, and myogenic differentiation media in the presence or absence of interleukin-1 and tumor necrosis factor (to simulate inflammatory microenvironment). The expression of active -catenin, p-GSK3, and GSK3 were detected by western blot and real-time polymerase chain reaction. The myogenic differentiation of LM-MSCs in inflammatory microenvironment and the regulation by Dickkopf-1 (DKK1) were tested both in vivo and in vitro. Inflammatory microenvironment could suppress the osteogenesis, adipogenesis, and myogenesis of LM-MSCs. The Wnt/-catenin signaling pathway was activated during myogenesis in inflammatory microenvironment. The suppressed myogenic differentiation capability of LM-MSCs in inflammatory microenvironment was reversed by DKK1. By regulating the Wnt/-catenin signaling pathway, DKK1 can improve the myogenic differentiation of LM-MSCs in inflammatory microenvironment. Thus, the results of this study may help improve the efficacy of LM-MSCs injection therapy for vocal fold regeneration.