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

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.

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases

“…Annexin A1 is a phospholipid-binding, Ca 2+ -dependent protein regulating cell behavior by inhibiting autophagy (63), enhancing inflammation and apoptosis (14, 63), suppressing proliferation (43), etc. In the ECM, conflicting reports implicate annexin A1 in both improving fibroblast synthetic activity (26) and exerting antifibrotic effects (38), potentially suggestive of a context-dependent function for this molecule.…”

Knockdown of Annexin A1 induces apoptosis, causing G2/M arrest and facilitating phagocytosis activity in human leukemia cell lines

“…Based on this study, the expression of pro-caspase-3 and pro-caspase-9 showed a slight increase in certain cells however no cleavage of these caspases was observed. Feng et al demonstrated that silencing of ANXA1 reduced apoptosis by upregulating Bcl-2 and procaspase-3 levels while downregulating the expression of cleaved caspase-3 in trophoblasts from preeclampsia rat's placenta tissue (16). The cleavage of caspase-9 and caspase-3 in this study was not observed probably due to approximately 10 min of caspase activation when there was a trigger of cell destruction.…”

Annexin A1 accounts for an anti-inflammatory binding target of sesamin metabolites

“…Although the exact reason has been unclear, recent reports suggested that suppression of ANX A1 expression interferes with apoptotic cell death in several cell lines. [44][45][46] These suggest that systematic disruption of ANX A1 expression in mice may contribute to protect against the CCl4induced cell death in the liver via distinct mechanisms from ANX A1 activation by sesamin metabolites. Based on the current results, a model for the mechanism of action of SC1 in monocytes is illustrated (Fig.…”