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Blockade of AT1 receptor restore the migration of vascular smooth muscle cells in high sodium medium

机译:封锁AT1受体恢复高钠培养基中血管平滑肌细胞的迁移

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Abstract The present study aimed to test the hypothesis that increased sodium concentration affects the migratory phenotype of vascular smooth muscle cells (VSMCs) independently of the haemodynamic factors. Cell migration was evaluated by wound‐healing assay under the following conditions: high sodium (HS, 160?mM) and control (CT, 140?mM). Cell viability was assessed by annexin V and propidium iodide labeling. Cyclooxygenase‐2 (COX‐2) gene expression was analysed by reverse transcription polymerase chain reaction. ERK1/2 phosphorylation was assessed by western blot. Exposure of VSMCs to HS reduced migration, and AT1R blockade prevented this response. HS increased COX‐2 gene expression, and COX‐2 blockade prevented the reduction in VSMC migration induced by HS. HS also increased ERK1/2 phosphorylation, and ERK1/2 inhibition recovered VSMC migration as well as blocked COX‐2 gene expression. The TXA 2 receptor blocker, but not the prostacyclin receptor blocker, prevented the HS‐induced VSMCs migration decrease. HS reduces the migration of VSMCs by increasing COX‐2 gene expression via AT1R‐ERK1/2 phosphorylation. In addition, increased COX‐2 by HS seems to modulate the reduction of VSMCs migration by the TXA 2 receptor.
机译:摘要目前的研究旨在测试钠浓度增加影响血管平滑肌细胞(VSMC)的迁徙表型的假设,独立于血管动力因子。在下列条件下通过伤口愈合测定评估细胞迁移:高钠(HS,160×mm)和对照(CT,140Ωmm)。通过膜蛋白V和碘化丙锭标记评估细胞活力。通过逆转录聚合酶链式反应分析环加氧基酶-2(COX-2)基因表达。 ERK1 / 2通过Western印迹评估磷酸化。 VSMC的曝光降低了迁移,并阻止了这种响应。 HS增加了COX-2基因表达,COX-2阻断阻止了HS诱导的VSMC迁移的降低。 HS还增加了ERK1 / 2磷酸化,ERK1 / 2抑制回收了VSMC迁移以及封闭的COX-2基因表达。 TXA 2受体阻滞剂,但不是前列环素受体阻滞剂,阻止了HS诱导的VSMC迁移减少。 HS通过AT1R-ERK1 / 2磷酸化增加COX-2基因表达来减少VSMC的迁移。此外,HS的增加的COX-2似乎调节TXA 2受体的VSMCs迁移的减少。

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