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.
- MeSH
- aktivace makrofágů MeSH
- fibróza * MeSH
- ledviny patologie metabolismus MeSH
- makrofágy * metabolismus patologie MeSH
- mikro RNA * metabolismus genetika MeSH
- myši inbrední C57BL * MeSH
- myši knockoutované MeSH
- myši MeSH
- proteiny vázající RNA * metabolismus genetika MeSH
- RAW 264.7 buňky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The pathogenesis of hepatic encephalopathy (HE) has been generally linked to blood ammonia, gamma-aminobutyric acid and serotonin. However, the exact mechanism remains unclear. In the present study, we aimed to explore the role of hippocampal dopamine (DA) and its receptors in the pathogenesis of HE through the use of behavioral testing, western blotting, and immunofluorescence staining in normal rats, HE model rats and rats treated with the DA precursor-levodopa (L-DOPA). HE model rats manifested fibrotic livers and showed serious behavioral disorders. They also had significantly lower hippocampal DA content and increased expression of both D1 and D2 receptors relative to normal rats. After treatment with L-DOPA, the HE model rats showed normal behavior and expression of D1 returned to normal levels. Furthermore, pretreatment with the D1 antagonist SCH23390 blocked the therapeutic effect of L-DOPA on behavior in HE model rats. Taken together, these results clarify that the decrease in hippocampal DA plays a role in the pathogenesis of HE and that this effect is mediated by D1. These findings provide new evidence for the pathogenesis of HE.
- MeSH
- dopamin metabolismus MeSH
- hipokampus metabolismus patologie MeSH
- jaterní encefalopatie metabolismus patologie MeSH
- játra patologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani Sprague-Dawley MeSH
- receptory dopaminu D1 metabolismus MeSH
- receptory dopaminu D2 metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
