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Published on: May 21, 2015
A link between the interleukin-6/Stat3 anti-apoptotic pathway and microRNA-21 in preimplantation mouse embryos
Xing-Hui Shen1, Young-Joon Han, Ding-Xiao Zhang
1Department of Animal Sciences, Chungbuk National University, Gaesin-dong Cheongju, Chungbuk 361-763, South Korea.
Abstract:
Signal transducers and activators of transcription-3 (Stat3) plays a central role in interleukin-6 (IL-6)-mediated cell proliferation by inhibiting apoptosis in a variety of cell types. MicroRNA-21 (miRNA-21), a ubiquitous miRNA, acts as an anti-apoptotic factor that seems to be indirectly but strictly linked to Stat3. In order to determine whether the IL-6 induced Stat3 anti-apoptosis pathway is linked with miRNA-21, we first determined the effects of recombinant mouse IL-6 on Stat3 expression, mouse embryo viability, and the mRNA levels of apoptosis related genes and miRNA-21 during mouse embryo development in vitro. Addition of 10 or 100 ng/ml of recombinant IL-6 to the culture medium did not affect the developmental ability of 2-cell stage embryos into blastocysts. However, total cell number was significantly increased and apoptosis was reduced in blastocyst stage embryos cultured in the presence of 100 ng/ml of recombinant IL-6. Furthermore, addition of recombinant IL-6 to the culture medium significantly increased the copy numbers of anti-apoptotic miRNA-21, up-regulated Bcl2l1, and down-regulated casp3. Similarly, the injection of mature miRNA-21 into cells up-regulated Bcl2l1 and down-regulated casp3. These results suggest that the induction of the Stat3 anti-apoptotic pathway by IL-6 is linked to miRNA-21 expression, which possibly results in the regulation of cell apoptosis in early mouse embryo development.
Insights
Interleukin-6 (IL-6) promotes early mouse embryo development by activating Signal Transducers and Activators of Transcription-3 (Stat3) and increasing anti-apoptotic microRNA-21 (miRNA-21) levels, reducing cell death.
Area of Science:
- Developmental Biology
- Molecular Biology
- Gene Regulation
Background:
- Signal transducers and activators of transcription-3 (Stat3) mediates interleukin-6 (IL-6) signaling, inhibiting apoptosis.
- MicroRNA-21 (miRNA-21) is an anti-apoptotic factor potentially linked to Stat3 activity.
- Understanding the interplay between IL-6, Stat3, and miRNA-21 is crucial for early embryonic development.
Purpose of the Study:
- To investigate the link between IL-6-induced Stat3 anti-apoptotic pathway and miRNA-21 during mouse embryonic development.
- To determine the effects of IL-6 on Stat3 expression, embryo viability, and apoptosis-related gene/miRNA-21 levels in vitro.
- To elucidate the role of miRNA-21 in regulating apoptosis during early embryogenesis.
Main Methods:
- Culture of 2-cell stage mouse embryos in vitro with varying concentrations of recombinant mouse IL-6.
- Assessment of embryo development to blastocyst stage, total cell number, and apoptosis.
- Quantification of Stat3 expression, apoptosis-related genes (Bcl2l1, casp3), and miRNA-21 levels.
- Direct injection of mature miRNA-21 into cells to assess its effects on gene expression.
Main Results:
- IL-6 (100 ng/ml) significantly increased blastocyst cell number and reduced apoptosis without affecting developmental potential.
- Recombinant IL-6 up-regulated anti-apoptotic miRNA-21 and Bcl2l1, while down-regulating casp3.
- miRNA-21 injection also led to Bcl2l1 up-regulation and casp3 down-regulation.
- IL-6 treatment increased Stat3 expression and miRNA-21 copy numbers.
Conclusions:
- IL-6-induced Stat3 anti-apoptotic pathway is closely associated with miRNA-21 expression during early mouse embryo development.
- miRNA-21 plays a role in regulating apoptosis in developing mouse embryos.
- This study highlights a novel regulatory mechanism involving IL-6, Stat3, and miRNA-21 in embryonic development.
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