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Published on: November 30, 2013
MiR-92a-3p Promotes Renal Injury and Fibrosis Through Facilitating M1 Macrophage Polarization via Targeting LIN28A
1Blood Purification Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Xiuying District, Haikou, Hainan Province, China. annacn08@163.com.
Abstract:
Infiltrated and activated M1 macrophages play a role in kidney injury and fibrosis during chronic kidney disease (CKD) progression. However, the specific ways that M1 macrophage polarization contributes to renal fibrosis are not fully understood. The study seeks to investigate how miR-92a-3p regulates M1 macrophage polarization and its connection to renal fibrosis in the development of CKD. Our results revealed that miR-92a-3p overexpression increased M1-macrophage activation, iNOS, IL-6, and TNF-alpha expression in RAW264.7 upon LPS stimulation. LIN28A overexpression reversed these effects. Moreover, miR-92a-3p overexpression in RAW264.7 exacerbated NRK-52E cell apoptosis induced by LPS, but LIN28A overexpression counteracted this effect. MiR-92a-3p knockout in unilateral ureteral obstruction (UUO) C57BL/6 mice led to reduced renal infiltration and fibrosis, accompanied by decreased iNOS, alpha-SMA, IL-6, TNF-alpha, and increased LIN28A. In summary, our findings suggest that miR-92a-3p may play a role in promoting renal injury and fibrosis both in vitro and in vivo. This effect is potentially achieved by facilitating M1 macrophage polarization through the targeting of LIN28A.
Insights
MicroRNA-92a-3p promotes kidney injury and fibrosis in chronic kidney disease (CKD) by enhancing M1 macrophage activation. Targeting this microRNA may offer a therapeutic strategy for mitigating renal fibrosis.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- M1 macrophages and their polarization are implicated in kidney injury and fibrosis in chronic kidney disease (CKD).
- The precise mechanisms by which M1 macrophage polarization drives renal fibrosis remain incompletely understood.
- Understanding the role of specific microRNAs in regulating M1 macrophage polarization is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of miR-92a-3p in regulating M1 macrophage polarization.
- To explore the association between miR-92a-3p, M1 macrophages, and renal fibrosis in the context of CKD.
- To identify potential therapeutic targets for mitigating kidney fibrosis.
Main Methods:
- In vitro studies using RAW264.7 and NRK-52E cell lines stimulated with lipopolysaccharide (LPS).
- Overexpression and knockout of miR-92a-3p and LIN28A in cell culture models.
- In vivo studies utilizing a unilateral ureteral obstruction (UUO) mouse model.
- Assessment of macrophage polarization markers (iNOS, IL-6, TNF-alpha), fibrosis markers (alpha-SMA), and cell apoptosis.
Main Results:
- miR-92a-3p overexpression enhanced M1 macrophage activation and pro-inflammatory cytokine expression (iNOS, IL-6, TNF-alpha) in vitro.
- LIN28A overexpression counteracted the effects of miR-92a-3p, reducing M1 polarization and subsequent renal cell apoptosis.
- In vivo, miR-92a-3p knockout in UUO mice significantly reduced renal infiltration, fibrosis, and inflammatory markers, while increasing LIN28A expression.
Conclusions:
- miR-92a-3p promotes renal injury and fibrosis in both in vitro and in vivo models of kidney disease.
- The pro-fibrotic effects of miR-92a-3p appear to be mediated by enhancing M1 macrophage polarization, potentially through targeting LIN28A.
- Targeting miR-92a-3p represents a potential therapeutic strategy for managing chronic kidney disease and its associated fibrosis.
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