MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization
Xiaoxiao Zhu1, Haiping Liu2, Zhen Zhang1
1Laboratory for Molecular Immunology, Institute of Basic Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 18877 Jingshi Road, Jinan 250062, Shandong, China.
Abstract:
Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear. MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated. In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derived M1 macrophages upon IFNγ and LPS stimulation. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1. Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects. Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa. miR-103 regulated STAT1 expression by direct binding to its 3'-UTR. Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively. Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway. miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.
Insights
Decreased miR-103 levels are linked to recurrent spontaneous abortion (RSA) by promoting M1 macrophage polarization. This microRNA may serve as a diagnostic marker and therapeutic target for RSA.
Area of Science:
- Immunology
- Reproductive Biology
- Molecular Biology
Background:
- Recurrent spontaneous abortion (RSA) is a common pregnancy complication.
- M1 macrophages are implicated in RSA pathogenesis, but mechanisms are unclear.
- MicroRNAs regulate macrophage polarization and are involved in RSA.
Purpose of the Study:
- Investigate the role of microRNAs in M1 macrophage differentiation in RSA.
- Determine the regulatory effect of miR-103 on M1 polarization in RSA.
- Explore miR-103 as a potential diagnostic and therapeutic target for RSA.
Main Methods:
- MiRNA microarray and qRT-PCR to analyze miR-103 expression in RSA patients and macrophages.
- In vitro experiments to assess the effect of miR-103 overexpression/inhibition on M1 polarization and STAT1/IRF1 pathway.
- In vivo studies in mice to evaluate the impact of miR-103 on embryo resorption and M1 polarization.
Main Results:
- miR-103 was significantly decreased in M1 macrophages and RSA patients, correlating negatively with STAT1.
- Down-regulation of miR-103 effectively discriminated RSA from normal pregnancies.
- Overexpression of miR-103 suppressed M1 polarization by inhibiting the STAT1/IRF1 pathway; miR-103 directly targets STAT1.
- In vivo, miR-103 overexpression reduced embryo resorption and M1 polarization.
Conclusions:
- Decreased miR-103 contributes to RSA by enhancing M1 macrophage polarization via the STAT1/IRF1 pathway.
- miR-103 shows potential as a diagnostic biomarker for RSA.
- miR-103 represents a promising therapeutic target for managing RSA.
