Research Paper Volume 16, Issue 4 pp 3790—3802
MUC1 promotes RIF by regulating macrophage ROS-SHP2 signaling pathway to up-regulate inflammatory response and inhibit angiogenesis
- 1 Department of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang 050017, China
- 2 Department of Obstetrics and Gynecology, Bethune International Peace Hospital, Shijiazhuang 050082, Hebei, China
- 3 Department of Reproductive Medicine Centre, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang 050017, China
Received: July 14, 2023 Accepted: December 19, 2023 Published: February 26, 2024
https://doi.org/10.18632/aging.205560How to Cite
Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: To explore the effect of MUC1 on recurrent implantation failure (RIF) and its molecular mechanism.
Methods: Bioinformation analysis was used to find possible molecular mechanisms of specific genes in the pathogenesis of RIF. The number of M1 and M2 macrophages was measured by flow cytometry. Immunohistochemical staining and western blotting were used to detect the expression of related proteins. Angiogenesis capacity was measured by cell tube-formation assay.
Results: Bioinformatics analysis results suggest that MUC1 may play an important role in RIF. The results of flow cytometry showed that compared with NC group, M1 macrophages increased significantly and M2 macrophages decreased significantly in MUC1 OE group. The results of immunohistochemical staining showed that MUC1 could inhibit the expression of VEGF. Western blotting results showed that MUC1 could significantly increase the expression of P22, P47, gp91, p-TBK1, IFNγ and IL-1β, and decrease the expression of p-SHP2, p-PI3K, p-mTOR, HIF1α and VEGF. After the addition of ROS inhibitor and PI3K inhibitor, the effect of MUC1 on the above proteins was eliminated. The results of tube formation experiments showed that MUC1 could inhibit vascular formation.
Conclusion: As a promising biomarker for the diagnosis of RIF, MUC1 can promote RIF by regulating macrophage ROS-SHP2 signaling pathway to up-regulate inflammatory response and inhibit angiogenesis.