TGF-β1可激活中性粒细胞信号传递和基因表达,但不能激活迁移
bioRxiv : the preprint server for biology
|June 9, 2023
概括
转化生长因子-β (TGF-β) 激活中性粒细胞的信号通路,但不会直接诱导迁移. 然而,瘤受条件的介质会促使中性粒细胞分泌放大招募的因素,影响癌症的进展.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 与瘤相关的中性粒细胞往往与癌症的不良结果相关.
- 转化生长因子-β (TGF-β) 在瘤微环境中被怀疑会促进前瘤中性粒细胞表型,但其对中性粒细胞信号传递和迁移的确切影响尚不清楚.
研究的目的:
- 研究TGF-β对中性粒细胞信号传递和迁移的影响.
- 为了确定TGF-β是否直接诱导中性粒细胞化学反应.
- 探索TGF-β对中性粒细胞基因表达和媒介分泌的影响.
主要方法:
- 使用了人类初级中性粒细胞和HL-60细胞系.
- 进行过井和下迁移测定.
- 分析了SMAD3和ERK1/2信号通路.
- 量化白血素B4 (LTB4) 的分泌.
- 进行RNA测序以评估基因表达变化.
主要成果:
- 在中性粒细胞中,TGF-β1激活了正规 (SMAD3) 和非正规 (ERK1/2) 信号.
- TGF-β1没有直接诱导中性粒细胞迁移或LTB4分泌.
- 瘤条件介质 (TCM) 诱导了SMAD3激活和LTB4分泌.
- TGF-β1和TCM改变了基因表达,包括上素M (OSM) 和血管内皮生长因子A (VEGFA) 的mRNA水平.
结论:
- TGF-β1对中性粒细胞有复杂的影响,激活关键信号通路,但不直接驱动迁移.
- 瘤微环境因素,包括条件介质中的TGF-β1,可以调节中性粒细胞的行为和基因表达,可能导致瘤进展.
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