ArticleJournal of translational medicine2024
Upregulation of Siglec-6 induces mitochondrial dysfunction by promoting GPR20 expression in early-onset preeclampsia.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- HIF-1α-mediated inhibition of the sFlt-1/sENG/TNF-α pathway promotes angiogenesis to ameliorate pre-eclampsia.Journal of molecular histology · 2025Article
- GPR56 function as a key repressor in hepatocyte pyroptosis and the pathogenesis of liver fibrosis.Journal of translational medicine · 2025Article
- Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6 and SHP2 induced Src and ERK signaling activation.Scientific reports · 2025Article
- Proteome-Based Maternal Plasma and Serum Biomarkers for Preeclampsia: A Systematic Review and Meta-Analysis.Life (Basel, Switzerland) · 2025Review
- SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs.Scientific reports · 2025Article
- A Multi-Algorithm Machine Learning Model for Predicting the Risk of Preterm Birth in Patients with Early-Onset Preeclampsia.International journal of general medicine · 2025Article
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12 authors.
Funding
Abstract
backgroundPreeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated.
methodsThe expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells.
resultsThe expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model.
conclusionsThis study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.
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