Atrial natriuretic peptide promotes uterine decidualization and a TRAIL-dependent mechanism in spiral artery remodeling
Wei Zhang, Shuo Li, Jinglei Lou, Hui Li, Meng Liu, Ningzheng Dong, Qingyu Wu
Wei Zhang, Shuo Li, Jinglei Lou, Hui Li, Meng Liu, Ningzheng Dong, Qingyu Wu
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Research Article Vascular biology

Atrial natriuretic peptide promotes uterine decidualization and a TRAIL-dependent mechanism in spiral artery remodeling

Abstract

Atrial natriuretic peptide (ANP) is an important hormone in cardiovascular biology. It is activated by the protease corin. In pregnancy, ANP and corin promote uterine spiral artery remodeling, but the underlying mechanism remains unknown. Here we report an ANP function in uterine decidualization and TNF-related apoptosis-inducing ligand–dependent (TRAIL-dependent) death in spiral arterial smooth muscle cells (SMCs) and endothelial cells (ECs). In ANP- or corin-deficient mice, uterine decidualization markers and TRAIL expression were decreased, whereas in cultured human endometrial stromal cells (HESCs), ANP increased decidualization and TRAIL expression. In uterine spiral arteries from pregnant wild-type mice, SMC and EC loss occurred sequentially before trophoblast invasion. In culture, TRAIL from decidualized HESCs induced apoptosis in uterine SMCs, but not in ECs with low TRAIL receptor expression. Subsequently, cyclophilin B was identified from apoptotic SMCs that upregulated endothelial TRAIL receptor and caused apoptosis in ECs. These results indicate that ANP promotes decidualization and TRAIL expression in endometrial stromal cells, contributing to sequential events in remodeling of spiral arteries, including SMC death and cyclophilin B release, which in turn induces TRAIL receptor expression and apoptosis in ECs.

Authors

Wei Zhang, Shuo Li, Jinglei Lou, Hui Li, Meng Liu, Ningzheng Dong, Qingyu Wu

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Figure 6

ANP upregulates TRAIL in dHESCs and uteri in pregnant mice.

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ANP upregulates TRAIL in dHESCs and uteri in pregnant mice. (A) Western ...
(A) Western blotting of TRAIL in HESCs and dHESCs cultured without (–) or with (+) recombinant ANP (1 nM). Quantitative data are shown in the bar graph (n = 5 per group). (B) Viability (top) and caspase-3 activity (bottom) in uterine SMCs treated with CM from HESCs or dHESCs without (–) or with (+) ANP pretreatment (n = 5 per group). (C) Viability of HUtMECs treated with CM from HESCs or dHESCs without (–) or with (+) ANP pretreatment (n = 3 per group). (D) Viability of HUtMECs treated with CM from SMCs that were incubated with CM from HESCs or dHESCs without (–) or with (+) ANP pretreatment (n = 3 per group). (E) Western blotting of uterine TRAIL in non-pregnant (NP) or pregnant (GD12.5) WT, Nppa–/–, and Corin–/– mice. Quantitative data are shown in the bar graph (n = 4 per group). (F) TRAIL staining in GD12.5 uteri from WT, Nppa–/–, and Corin–/– mice. Immunoglobulin (Ig) was a control. (G) A proposed model. ANP enhances decidualization and upregulates TRAIL in uterine stromal cells. TRAIL induces SMC death (†), leading to cyclophilin B (CyPB) release, which in turn upregulates TRAIL receptor (TRAILR) in ECs, causing EC death (†) in spiral arteries. All quantitative data are mean ± SD and were analyzed by 1-way ANOVA (A, B, D, and E) or Kruskal-Wallis test (C). *P < 0.05; **P < 0.01.