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Abstract：
The Wnt signaling pathway has been implicated in the pathogenesis of fibrotic disorders and malignancies. Hence, we aimed to assess the potential of the induced pluripotent stem cells (IPS) in modulating the expression of the cardinal genes of the Wnt pathway in a mouse model of idiopathic pulmonary fibrosis (IPF).
C57Bl/6 mice were randomly divided into three groups of Control, Bleomycin (BLM), and BLM + IPS; the BLM mice received intratracheal instillation of bleomycin, BLM + IPS mice received tail vein injection of IPS cells 48 h post instillation of the BLM; The Control group received Phosphate-buffered saline instead. After 3 weeks, the mice were sacrificed and Histologic assessments including hydroxy proline assay, Hematoxylin and Eosin, and Masson-trichrome staining were performed. The expression of the genes for Wnt, β-Catenin, Lef, Dkk1, and Bmp4 was assessed utilizing specific primers and SYBR green master mix.
Histologic assessments revealed that the fibrotic lesions and inflammation were significantly alleviated in the BLM + IPS group. Besides, the gene expression analyses demonstrated the upregulation of Wnt, β-Catenin, and LEF along with the significant downregulation of the Bmp4 and DKK1 in response to bleomycin treatment; subsequently, it was found that the treatment of the IPF mice with IPS cells results in the downregulation of the Wnt, β-Catenin, and Lef, as well as upregulation of the Dkk1, but not the Bmp4 gene (P values < 0.05).
The current study highlights the therapeutic potential of the IPS cells on the IPF mouse model in terms of regulating the aberrant expression of the factors contributing to the Wnt signaling pathway.
C57Bl/6 mice were randomly divided into three groups of Control, Bleomycin (BLM), and BLM + IPS; the BLM mice received intratracheal instillation of bleomycin, BLM + IPS mice received tail vein injection of IPS cells 48 h post instillation of the BLM; The Control group received Phosphate-buffered saline instead. After 3 weeks, the mice were sacrificed and Histologic assessments including hydroxy proline assay, Hematoxylin and Eosin, and Masson-trichrome staining were performed. The expression of the genes for Wnt, β-Catenin, Lef, Dkk1, and Bmp4 was assessed utilizing specific primers and SYBR green master mix.
Histologic assessments revealed that the fibrotic lesions and inflammation were significantly alleviated in the BLM + IPS group. Besides, the gene expression analyses demonstrated the upregulation of Wnt, β-Catenin, and LEF along with the significant downregulation of the Bmp4 and DKK1 in response to bleomycin treatment; subsequently, it was found that the treatment of the IPF mice with IPS cells results in the downregulation of the Wnt, β-Catenin, and Lef, as well as upregulation of the Dkk1, but not the Bmp4 gene (P values < 0.05).
The current study highlights the therapeutic potential of the IPS cells on the IPF mouse model in terms of regulating the aberrant expression of the factors contributing to the Wnt signaling pathway.
摘要：
背景：Wnt信号通路与纤维化疾病和恶性肿瘤的发病机制有关。因此，我们旨在评估诱导性多能干细胞(IPS)在特发性肺纤维化(IPF)小鼠模型中调节Wnt通路主要基因表达的潜力.
方法：C57Bl/6小鼠随机分为3组对照组,博来霉素（BLM），和BLM+IPS；BLM小鼠接受气管内滴注博来霉素，BLM+IPS小鼠在BLM滴注后48小时接受IPS细胞的尾静脉注射;对照组接受磷酸盐缓冲盐水代替。3周后,处死小鼠，进行组织学评估，包括羟脯氨酸测定，苏木精和伊红,并进行了Masson三色染色。Wnt基因的表达，β-连环蛋白，Lef,利用特异性引物和SYBR绿色主混合物评估Dkk1和Bmp4。
结果：组织学评估显示BLM+IPS组纤维化病变和炎症明显减轻。此外,基因表达分析证实了Wnt的上调，β-连环蛋白，和LEF以及响应博来霉素治疗的Bmp4和DKK1的显着下调；随后，发现用IPS细胞治疗IPF小鼠导致Wnt下调，β-连环蛋白，还有Lef,以及Dkk1的上调，但Bmp4基因不上调（P值<0.05）。
结论：本研究强调了IPF小鼠模型中IPS细胞在调节Wnt信号通路因子异常表达方面的治疗潜力。
方法：C57Bl/6小鼠随机分为3组对照组,博来霉素（BLM），和BLM+IPS；BLM小鼠接受气管内滴注博来霉素，BLM+IPS小鼠在BLM滴注后48小时接受IPS细胞的尾静脉注射;对照组接受磷酸盐缓冲盐水代替。3周后,处死小鼠，进行组织学评估，包括羟脯氨酸测定，苏木精和伊红,并进行了Masson三色染色。Wnt基因的表达，β-连环蛋白，Lef,利用特异性引物和SYBR绿色主混合物评估Dkk1和Bmp4。
结果：组织学评估显示BLM+IPS组纤维化病变和炎症明显减轻。此外,基因表达分析证实了Wnt的上调，β-连环蛋白，和LEF以及响应博来霉素治疗的Bmp4和DKK1的显着下调；随后，发现用IPS细胞治疗IPF小鼠导致Wnt下调，β-连环蛋白，还有Lef,以及Dkk1的上调，但Bmp4基因不上调（P值<0.05）。
结论：本研究强调了IPF小鼠模型中IPS细胞在调节Wnt信号通路因子异常表达方面的治疗潜力。
