Prevention of the Progression of lupus Nephritis in MRL/lpr Mice by Modulating miR-9-5p/Foxo1 Axis.

Abstract

MiR-9-5p is up-regulated in lupus nephritis (LN) patients and targets Foxo1 that is a protective factor against renal disorders. In the current study, the role of miR-9-5p/Foxo1 LN progression was assessed and the associated mechanism was explored. The levels of LN-associated miRs were firstly detected in MRL/lpr mice. Then the effect of miR-9-5p modulation on the viability of SV40 MES 13 cells was detected. MRL/lpr mice were treated with miR agomirs or antagonists, and effects on renal structure and function were assessed. MiR-9-5p was selected as the potential target, which was up-regulated in MRL/lpr mice, contributing to the suppressed expression of Foxo1. The modulation of miR-9-5p in vitro influenced the viability of SV40 MES 13 cells. The progression of LN in mice was also associated with the increased level of miR-9-5p and the decreased level of Foxo1. The administration of miR agomirs significantly impaired renal structure and function impairments associated with LN, along with the suppressed expression of Foxo1, while antagonists improved these features by up-regulating Foxo1 level. The current study demonstrated that miR-9-5p showed LN promoting effects, which depended on the inhibition of Foxo1.