Mucin1 induced trophoblast dysfunction in gestational diabetes mellitus via Wnt/β-catenin pathway

• Verfasst von: Cui, Shuang-Shuang [VerfasserIn]
• Verfasst von: Zhang, Ping [VerfasserIn]
• Verfasst von: Sun, Lu [VerfasserIn]
• Verfasst von: Yuan, Yu-Lin-Lan [VerfasserIn]
• Verfasst von: Wang, Jingyun [VerfasserIn]
• Verfasst von: Zhang, Feng-Xiang [VerfasserIn]
• Verfasst von: Li, Ruiman [VerfasserIn]
• Titel: Mucin1 induced trophoblast dysfunction in gestational diabetes mellitus via Wnt/β-catenin pathway
• Verf.angabe: Shuang-Shuang Cui, Ping Zhang, Lu Sun, Yu-Lin-Lan Yuan, Jingyun Wang, Feng-Xiang Zhang and Ruiman Li
• E-Jahr: 2023
• Jahr: 22 August 2023
• Umfang: 14 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 15.10.2024
• Titel Quelle: Enthalten in: Biological research
• Ort Quelle: Santiago : [Verlag nicht ermittelbar], 1999
• Jahr Quelle: 2023
• Band/Heft Quelle: 56(2023), 1, Seite 1-14
• ISSN Quelle: 0717-6287
• DOI: doi:10.1186/s40659-023-00460-3
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1905676875

Abstract

To elucidate the role of Mucin1 (MUC1) in the trophoblast function (glucose uptake and apoptosis) of gestational diabetes mellitus (GDM) women through the Wnt/β-catenin pathway. Glucose uptake was analyzed by plasma GLUT1 and GLUT4 levels with ELISA and measured by the expression of GLUT4 and INSR with immunofluorescence and Western blotting. Apoptosis was measured by the expression of Bcl-2 and Caspase3 by Western blotting and flow cytometry. Wnt/β-catenin signaling measured by Western blotting. In vitro studies were performed using HTR-8/SVneo cells that were cultured and treated with high glucose (HG), sh-MUC1 and FH535 (inhibitor of Wnt/β-catenin signaling). MUC1 was highly expressed in the placental trophoblasts of GDM, and the Wnt/β-catenin pathway was activated, along with dysfunction of glucose uptake and apoptosis. MUC1 knockdown resulted in increased invasiveness and decreased apoptosis in trophoblast cells. The initial linkage between MUC1, the Wnt/β-catenin pathway, and glucose uptake was confirmed by using an HG-exposed HTR-8/SVneo cell model with MUC1 knockdown. MUC1 knockdown inhibited the Wnt/β-catenin signaling pathway and reversed glucose uptake dysfunction and apoptosis in HG-induced HTR-8/SVneo cells. Meanwhile, inhibition of Wnt/β-catenin signaling could also reverse the dysfunction of glucose uptake and apoptosis. In summary, the increased level of MUC1 in GDM could abnormally activate the Wnt/β-catenin signaling pathway, leading to trophoblast dysfunction, which may impair glucose uptake and induce apoptosis in placental tissues of GDM women.