MiR-663a/MiR-423-5p are involved in the pathogenesis of lupus nephritis via modulating the activation of NF-κB by targeting TNIP2.

Lupus nephritis (LN) is a kidney disorder resulting from systemic lupus erythematosus (SLE), an autoimmune inflammatory disease. MicroRNAs (miRNAs) have emerged as a new class of therapeutic targets in LN treatment, but how they specifically contribute to the disease development remains unknown. In this study, the expression of miR-663a/miR-423-5p and TNIP2 were compared between human renal biopsy tissues from LN patients and renal cell carcinoma patients. Additionally, the LN mouse model was used to measure the levels of miR-663a/miR-423-5p and TNIP2 in the control group and the experiment group. Dual luciferase reporter assay was used to validate TNIP2 as the target of miR-663a/miR-423-5p. MiR-663a/miR-423-5p were highly expressed in kidney tissues from LN patients as compared to kidney tissues from SLE patients and normal tissues. TNIP2 showed comparatively low expression in tissues from LN patients. In the LN mouse model, the levels of miR-663a/miR-423-5p were improved whereas TNIP2 was reduced in response to renal injury stimulated by pristine. MiR-663a/miR-423-5p mimics and inhibitors triggered decrease and increase of TNIP2 levels, respectively. Dual luciferase assay showed that TNIP2 was a direct target of miR-663a/miR-423-5p. In addition, detection of inflammatory factors confirmed that miR-663a/miR-423-5p and TNIP2 fundamentally contributed to LPS-induced NF-κB activation. Our findings suggested the involvement of miR-663a/miR-423-5p-TNIP2-NF-κB axis in the development of LN, thereby providing new therapeutic targets for LN treatment.