Problem: Preeclampsia (PE) is a unique gestational disorder leading to maternal and neonatal morbidity and mortality. AnnexinA7 (ANXA7) is a calcium-dependent phospholipid-binding protein that promotes membrane fusion during exocytosis. However, the function of ANXA7 in placental trophoblast is poorly understood. The present study aimed to investigate a possible association between ANXA7 and human trophoblast apoptosis.
Methods: We collected human placental tissues from patients with PE and normal pregnant women to elucidate the expression level of ANXA7. The ANXA7-knockdown and ANXA7-overexpressing HTR8/SVneo cells were utilized for studying the function of ANXA7 in trophoblast. The proliferation and apoptosis levels of trophoblast were examined with Western blot assay, flow cytometry, Cell Counting Kit-8 assay, and immunohistochemistry.
Results: ANXA7 expression was significantly lower in placentas from patients with PE patients compared with that in from normal pregnant controls. Knockdown of ANXA7 induced cell apoptosis and inhibited cell proliferation in HTR-8 via by downregulating BCL2 protein levels. Overexpression of ANXA7 reduced apoptosis and promoted HTR8 proliferation. Further analyses showed that ANXA7 knockdown inhibited the activation of the JAK1/STAT3 pathway in HTR-8 cells.
Conclusion: Our findings revealed a new regulatory pathway of ANXA7/JAK1/STAT3 in trophoblast apoptosis in preeclampsia, suggesting that ANXA7 is a potential therapeutic target for preeclampsia.
Keywords: ANXA7; Janus kinase 1; STAT3 transcription factor; apoptosis; cell proliferation; preeclampsia; trophoblasts.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.