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miR-21-5p-loaded bone mesenchymal stem cell-derived exosomes repair ovarian function in autoimmune premature ovarian
Yutao Yang1, Lichao Tang1, Yuanling Xiao1
1Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Research Question:
What is the effect of micro-RNA (miR)-21-5p-loaded bone marrow mesenchymal stem cell-derived exosomes (miR-21-Exo) on autoimmune premature ovarian insufficiency (POI)?
Design:
The Cell Counting Kit 8 (CCK8) assay, fluorescence-activated cell sorting, western blotting, quantitative reverse transcriptase (qRT)-PCR and enzyme-linked immunosorbent assay (ELISA) verified the effect of miR-21-Exo on interferon-γ (IFN-γ)-induced KGN cells. qRT-PCR, western blotting and dual-luciferase reporter gene assays verified that miR-21-Exo mediated Msh homeobox 1 (MSX1) regulation of the Notch signalling pathway and that miR-21 interacted directly with MSX1. The effects of miR-21-Exo on the ovaries were verified by monitoring of the oestrous cycle, haematoxylin and eosin staining, follicle counts, ELISA, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL), western blotting and qRT-PCR.
Results:
The results showed that miR-21-Exo promoted IFN-γ-induced KGN cell proliferation and hormone synthesis, and inhibited apoptosis. Using dual-luciferase reporter gene assays, miR-21 and MSX1 were shown to have direct interactions. Moreover, the findings elucidated that miR-21-Exo inhibited cell apoptosis and promoted hormone synthesis by mediating MSX1 to regulate the Notch signalling pathway. miR-21-Exo restored the ovarian structure in a mouse model of autoimmune POI, promoted endocrine function and proliferation, and inhibited apoptosis and inflammation in vivo.
Conclusions:
This study demonstrates that miR-21-Exo regulates the MSX1-mediated Notch signalling pathway to inhibit granulosa cell apoptosis and improve hormone synthesis function, providing insight into a potential mechanism of molecular therapy for the treatment of autoimmune POI.
Insights
Micro-RNA (miR)-21-5p-loaded exosomes (miR-21-Exo) from mesenchymal stem cells improve ovarian function in autoimmune premature ovarian insufficiency (POI). This therapy targets the MSX1-Notch pathway to reduce granulosa cell apoptosis and enhance hormone synthesis.
Area of Science:
- Reproductive biology
- Cell biology
- Molecular medicine
Background:
- Autoimmune premature ovarian insufficiency (POI) poses significant challenges in reproductive health.
- Understanding the molecular mechanisms underlying POI is crucial for developing effective therapies.
- Mesenchymal stem cell-derived exosomes show therapeutic potential in various diseases.
Purpose of the Study:
- To investigate the therapeutic effect of micro-RNA (miR)-21-5p-loaded bone marrow mesenchymal stem cell-derived exosomes (miR-21-Exo) on autoimmune premature ovarian insufficiency (POI).
- To elucidate the underlying molecular mechanisms involving Msh homeobox 1 (MSX1) and the Notch signalling pathway.
Main Methods:
- Cell Counting Kit 8 (CCK8) assay, fluorescence-activated cell sorting, western blotting, qRT-PCR, and ELISA were used to assess miR-21-Exo effects on KGN cells.
- Dual-luciferase reporter gene assays, qRT-PCR, and western blotting were employed to verify the interaction between miR-21 and MSX1 and pathway regulation.
- In vivo studies in a mouse model of autoimmune POI included oestrous cycle monitoring, histological analysis (H&E), follicle counts, ELISA, immunohistochemistry, TUNEL assay, western blotting, and qRT-PCR.
Main Results:
- miR-21-Exo promoted proliferation and hormone synthesis while inhibiting apoptosis in interferon-γ (IFN-γ)-induced KGN cells.
- Direct interaction between miR-21 and MSX1 was confirmed, revealing miR-21-Exo's role in mediating MSX1 to regulate the Notch signalling pathway.
- In vivo, miR-21-Exo restored ovarian structure, enhanced endocrine function and proliferation, and reduced apoptosis and inflammation in autoimmune POI mice.
Conclusions:
- miR-21-Exo effectively treats autoimmune POI by regulating the MSX1-mediated Notch signalling pathway.
- This mechanism inhibits granulosa cell apoptosis and improves hormone synthesis, offering a novel molecular therapy approach for POI.
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