Reference - Detail
| RRC ID | 89891 |
|---|---|
| Author | Kandel M, Bartho L, Hannan NJ, Cannon P, Nguyen TV, Nguyen A, Murphy CN, Wong GP, Tong S, Kaitu'u-Lino TJ. |
| Title | Sialic acid-binding immunoglobulin-like lectin-6 (SIGLEC6) is increased by hypoxia and inflammation in trophoblasts. |
| Journal | Pregnancy Hypertens |
| Abstract |
OBJECTIVES:SIGLEC6, a human-specific transmembrane receptor, is highly expressed in placenta. SIGLEC6 is elevated in maternal circulation preceding preeclampsia and in women with preeclampsia, correlating with disease severity. This study aimed to investigate the regulatory mechanisms of placental SIGLEC6 and its involvement in processes associated with preeclampsia pathogenesis. STUDY DESIGN:To determine cell source, SIGLEC6 was measured in (cyto)trophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. We then assessed the impact of hypoxia (1% vs 8% Oxygen), inflammatory cytokines (Interleukin 6 (IL-6) or Tumour Necrosis Factor alpha (TNFα)), or Brefeldin A (impairs protein trafficking) on SIGLEC6 production/secretion. We also assessed whether treatment with recombinant SIGLEC6 induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). MAIN OUTCOMES MEASURES:SIGLEC6 expression across trophoblast subpopulations; its regulation under hypoxia, inflammation and Brefeldin A treatment; and its effect on endothelial dysfunction markers. RESULTS:SIGLEC6 was expressed in all cell types and upregulated during differentiation of human trophoblast stem cells into syncytiotrophoblasts and extravillous trophoblasts. Exposure of syncytiotrophoblasts to hypoxia elevated SIGLEC6 expression (p = 0.0079), and protein secretion (p = 0.0079). Similarly, pro-inflammatory cytokines increased SIGLEC6 expression (IL-6: p = 0.0016, and TNFα: p = 0.0015) and protein secretion (IL-6: p = 0.002, and TNFα: p = 0.01) from syncytiotrophoblasts. Treatment with Brefeldin A reduced SIGLEC6 secretion in cell lysates (p = 0.001) and conditioned media (p = 0.02). Recombinant SIGLEC6 had no effect on pro- and anti-angiogenic factors and endothelial dysfunction markers in HUVECs. CONCLUSION:SIGLEC6 expression is induced by hypoxia and inflammation in syncytialised hTSCs, but recombinant SIGLEC6 did not induce endothelial dysfunction in HUVECs. |
| Volume | 45 |
| Pages | 101503 |
| Published | 2026-8-13 |
| DOI | 10.1016/j.preghy.2026.101503 |
| PII | S2210-7789(26)00091-7 |
| PMID | 42600490 |
| Resource | |
| Human and Animal Cells | bTS5(RCB4940) bTS11(RCB4941) |