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miRNA-29c-3p Activates the JAK2/STAT3 Signaling Pathway by Down-Regulating SOCS3 to Promote Pathological Angiogenesis
Xiao-Mei Chen1, Min Wen1, Rong Wu2
1School of Medicine, Zunyi Medical University, Zunyi, Guizhou, China.
Objective:
The purpose of this study was to explore the effects and potential mechanisms of miRNA-29c-3p regulating suppressors of cytokine signaling 3 (SOCS3) in Diabetic Retinopathy (DR) progression.
Methods:
Human retinal microvascular endothelial cells (hRMECs) were exposed to 25 mM high glucose concentrations to establish a DR cell model and underwent transfection to down-regulate miRNA-29c-3p and SOCS3.
Results:
High glucose induces upregulation of miRNA-29c-3p and downregulation of SOCS3 expression in hRMECs. Under high-glucose conditions, inhibition of miRNA-29c-3p significantly suppresses hRMEC migration, angiogenesis, and the release of pro-inflammatory cytokines. Notably, this inhibitory effect is partially reversed upon SOCS3 knockdown. Moreover, miRNA-29c-3p directly targets and regulates SOCS3 mRNA expression. Importantly, SOCS3 knockdown markedly activates the JAK2/STAT3 signaling pathway in hRMECs, which can be suppressed by reducing miRNA-29c-3p levels.
Conclusion:
miRNA-29c-3p promotes DR progression by activating the JAK2/STAT3 pathway through SOCS3 regulation.
Insights
MicroRNA-29c-3p promotes diabetic retinopathy (DR) by targeting SOCS3 and activating the JAK2/STAT3 pathway. Inhibiting miRNA-29c-3p may offer a therapeutic strategy for DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a microvascular complication of diabetes.
- Understanding the molecular mechanisms of DR progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-29c-3p (miRNA-29c-3p) in regulating Suppressors of Cytokine Signaling 3 (SOCS3) in diabetic retinopathy (DR).
- To elucidate the potential mechanisms by which miRNA-29c-3p influences DR progression.
Main Methods:
- Established a DR cell model using human retinal microvascular endothelial cells (hRMECs) exposed to high glucose.
- Utilized transfection to down-regulate miRNA-29c-3p and SOCS3 expression.
- Analyzed cell migration, angiogenesis, pro-inflammatory cytokine release, and JAK2/STAT3 pathway activation.
Main Results:
- High glucose increased miRNA-29c-3p and decreased SOCS3 expression in hRMECs.
- Inhibiting miRNA-29c-3p suppressed hRMEC migration, angiogenesis, and pro-inflammatory cytokine release, effects partially reversed by SOCS3 knockdown.
- miRNA-29c-3p directly targets SOCS3 mRNA, and SOCS3 knockdown activates the JAK2/STAT3 pathway, which can be mitigated by reducing miRNA-29c-3p.
Conclusions:
- miRNA-29c-3p promotes DR progression by negatively regulating SOCS3.
- The mechanism involves the activation of the JAK2/STAT3 signaling pathway.
- Targeting miRNA-29c-3p or SOCS3 may represent a therapeutic approach for DR.
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