Tumour necrosis factor (TNF)-α activation of mesenchymal stromal cells (MSC) enhances their tumour-suppressive properties and tumour-homing ability. The molecular actors involved are unknown. We found that TNF induced MSC migration and tubulogenesis which correlated with a dose-dependent increase in Cavin-1 and Cavin-3 transcript levels. TNF triggered cyclooxygenase (COX)-2 expression, whereas specific siRNA-mediated gene silencing of Cavin-2 resulted in an amplified COX-2 expression, tubulogenesis, and migratory response partially due to a rapid and sustained increase in NF-κB phosphorylation status. Our results highlight a suppressive role for the caveolar component Cavin-2 in the angiogenic and inflammatory regulation of TNF-activated MSC.

中文翻译：

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Cavin-2在TNF诱导的间质基质细胞炎症和血管生成表型中起抑制调节剂的作用。

间充质基质细胞（MSC）的肿瘤坏死因子（TNF）-α激活可增强其肿瘤抑制特性和肿瘤归巢能力。所涉及的分子参与者是未知的。我们发现TNF诱导MSC迁移和肾小管生成，与Cavin -1和Cavin -3转录水平的剂量依赖性增加相关。TNF触发环氧合酶（COX）-2的表达，而特定的siRNA介导的基因沉默卡万-2导致扩增COX-2的表达，小管，和迁移反应部分地归因于NF-快速和持续增加κ乙磷酸化状态。我们的结果突显了海绵体成分Cavin的抑制作用-2在TNF激活的MSC的血管生成和炎症调节中。