Fibroblast growth factor-1-induced ERK1/2 signaling reciprocally regulates proliferation and smooth muscle cell differentiation of ligament-derived endothelial progenitor cell-like cells.
Fibroblast growth factor-1-induced ERK1/2 signaling reciprocally regulates proliferation and smooth muscle cell differentiation of ligament-derived endothelial progenitor cell-like cells.
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DOI：
10.3892/ijmm.2011.847
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发表时间：
2011-11
影响因子：
5.4
通讯作者：
Mikako Takahashi;N. Okubo;N. Chosa;N. Takahashi;Miho Ibi;M. Kamo;H. Mizuki;A. Ishisaki;S. Kyakumoto
中科院分区：
文献类型：
--
作者：
Mikako Takahashi;N. Okubo;N. Chosa;N. Takahashi;Miho Ibi;M. Kamo;H. Mizuki;A. Ishisaki;S. Kyakumoto
牙周膜（PDL）是位于牙根和牙槽骨之间的纤维结缔组织。我们先前证明，原代培养的PDL成纤维细胞的单细胞衍生培养物具有构建内皮细胞（EC）标记阳性血管样结构的潜力，这表明韧带组织中的成纤维细胞谱系细胞可以充当内皮祖细胞（EPC），其再生以在受损韧带组织周围构建血管系统。此外，我们发现EPC样成纤维细胞不仅表达EC标记，而且还表达平滑肌细胞（SMC）标记。通常，EC和SMC之间的相互作用调节血管发育和重塑，并且是形成成熟和功能性血管网络所必需的。然而，韧带来源的EPC样成纤维细胞的SMC分化的机制仍有待澄清。在这项研究中，我们发现，抑制成纤维细胞生长因子1（FGF-1）诱导的细胞外信号调节激酶1/2（ERK 1/2）信号与MAPK/ERK激酶（MEK）抑制剂U 0126完全废除FGF-1诱导的韧带衍生的EPC样成纤维细胞的增殖。此外，U 0126处理FGF-1刺激的韧带来源的EPC样成纤维细胞显著诱导细胞的SMC分化。因此，FGF-1诱导的ERK 1/2信号不仅促进了韧带来源的EPC样成纤维细胞的增殖，而且抑制了细胞的SMC分化，表明FGF-1通过ERK介导的信号调节EPC样细胞的增殖和SMC分化来控制韧带组织周围血管网络的构建。
The periodontal ligament (PDL) is a fibrous connective tissue located between the tooth root and the alveolar bone. We previously demonstrated that a single cell-derived culture of primarily cultured PDL fibroblasts has the potential to construct an endothelial cell (EC) marker-positive blood vessel-like structure, suggesting that the fibroblastic lineage cells in ligament tissue could act as the endothelial progenitor cells (EPCs), which regenerate to construct a vascular system around the damaged ligament tissue. Moreover, we showed that EPC-like fibroblasts expressed not only EC markers but also smooth muscle cell (SMC) markers. Generally, an interaction between ECs and SMCs regulates blood vessel development and remodeling, and is required for the formation of a mature and functional vascular network. However, the mechanism underlying the SMC differentiation of the ligament-derived EPC-like fibroblasts remains to be clarified. In this study, we showed that suppression of fibroblast growth factor 1 (FGF-1)-induced extracellular signal-regulated kinase 1/2 (ERK1/2) signaling with the MAPK/ERK kinase (MEK) inhibitor U0126 completely abolished the FGF-1-induced proliferation of the ligament-derived EPC-like fibroblasts. In addition, U0126 treatment of FGF-1-stimulated ligament-derived EPC-like fibroblasts significantly induced the SMC differentiation of the cells. Thus, FGF-1-induced ERK1/2 signaling not only promoted the proliferation of the ligament-derived EPC-like fibroblasts, but also suppressed the SMC differentiation of the cells, suggesting that FGF-1 controls the construction of a vascular network around the ligament tissue by regulating the proliferation and SMC differentiation of the EPC-like cells through ERK-mediated signaling.