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Published on: December 21, 2011
MUC1 promotes RIF by regulating macrophage ROS-SHP2 signaling pathway to up-regulate inflammatory response and
Rongna Liu1,2, Lin Chen1,2, Xin Zhao2
1Department of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang 050017, China.
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.
Insights
Mucin 1 (MUC1) promotes recurrent implantation failure (RIF) by increasing inflammatory responses and inhibiting blood vessel formation. MUC1 may serve as a diagnostic biomarker for RIF.
Area of Science:
- Reproductive immunology
- Molecular biology
- Cell biology
Background:
- Recurrent implantation failure (RIF) is a complex condition affecting fertility.
- Understanding the molecular mechanisms underlying RIF is crucial for developing effective diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the role of Mucin 1 (MUC1) in recurrent implantation failure (RIF).
- To elucidate the molecular mechanisms by which MUC1 influences RIF pathogenesis.
Main Methods:
- Bioinformatic analysis to identify potential molecular mechanisms.
- Flow cytometry to quantify macrophage populations (M1 and M2).
- Immunohistochemistry and Western blotting to assess protein expression.
- Cell tube-formation assay to evaluate angiogenesis capacity.
Main Results:
- Bioinformatics suggested MUC1's significant role in RIF.
- MUC1 overexpression increased M1 macrophages and decreased M2 macrophages.
- MUC1 inhibited VEGF expression and angiogenesis.
- MUC1 modulated key proteins in the ROS-SHP2 signaling pathway, including increased P22, P47, gp91, p-TBK1, IFNγ, IL-1β, and decreased p-SHP2, p-PI3K, p-mTOR, HIF1α, VEGF.
- Inhibitors of ROS and PI3K reversed MUC1's effects.
Conclusions:
- MUC1 promotes RIF by regulating the macrophage ROS-SHP2 signaling pathway.
- MUC1 up-regulates inflammatory responses and inhibits angiogenesis, contributing to RIF.
- MUC1 shows potential as a biomarker for RIF diagnosis.
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