Silencing of Annexin A1 suppressed the apoptosis and inflammatory response of preeclampsia rat trophoblasts

沉默 Annexin A1 可抑制先兆子痫大鼠滋养细胞凋亡和炎症反应

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作者:Jing Feng, Xinling Wang, Hongyan Li, Li Wang, Zengjun Tang

Abstract

Preeclampsia (PE) is a disorder that is characterized by pregnancy‑induced hypertension. It has been reported that Annexin A1 (ANXA1) is highly expressed in the plasma of women diagnosed with PE. Therefore, the present study aimed to examine the effect of ANXA1 on PE rats. The PE animal model was constructed in rats using Nω‑nitro‑L‑arginine methyl ester (L‑NAME), and the blood pressure and urine protein levels of rats were detected. The pathological features of placental tissue, and the levels of inflammatory factors and ANXA1 were respectively measured by hematoxylin‑eosin staining, enzyme‑linked immunosorbent assay and immunohistochemical assay. The activity of trophoblasts obtained from PE placental tissue was measured using immunofluorescence staining, while cell apoptosis was assessed using flow cytometry. The levels of associated factors were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The results identified that systolic blood pressure, diastolic blood pressure, mean arterial pressure and urine protein levels were enhanced, and that the contents of ANXA1, tumor necrosis factor alpha (TNF‑α), interleukin (IL)‑1β, IL‑6 and IL‑8 were increased in the L‑NAME group. Transfection with small interfering RNA (siRNA)‑ANXA1 markedly decreased the apoptosis and inflammatory response of trophoblasts. In addition, siRNA‑ANXA1 upregulated the levels of B‑cell lymphoma‑2 (Bcl‑2) and pro‑caspase‑3, and downregulated the levels of Bcl‑2‑associated X protein, cleaved‑caspase‑3, TNF‑α, IL‑1β, IL‑6 and IL‑8. Furthermore, siRNA‑ANXA1 repressed the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3); however, siRNA‑ANXA1 did not alter the levels of JAK2 and STAT3. Therefore, silencing of ANXA1 suppressed the apoptosis and inflammatory response of PE rat trophoblasts, and downregulated JAK2/STAK3 pathway.

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