Deletion of the miR-25/93/106b cluster induces glomerular deposition of immune complexes and renal fibrosis in mice.

Abstract

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is caused by immune system dysfunction and affects only the kidneys. miRNA was involved in IgAN, in which their roles are still unknown. Herein, we found increased glomerular medulla size, proteinuria, kidney artery resistance, kidney fibrosis and immune complex deposition in 5‐month miR‐25/93/106b cluster knockout (miR‐TKO) mice. In vitro, the inhibition of miR‐25 cluster could promote cell proliferation and increase fibrosis‐related protein and transferrin receptor (TFRC) expression in human renal glomerular mesangial cell (HRMC). Luciferase assay revealed that inhibition of miR‐93/106b cluster could upregulate Ccnd1 expression through direct binding with the 3’UTR of Ccnd1. Conversely, inhibition of Ccnd1 expression prevented miR‐93/106b‐induced effect in HRMC. These findings suggested that miR‐25 cluster played an important role in the progression of IgAN, which provided new insights into the pathogenesis and treatment of IgAN.