MiR-23b-3p exerts a protective effect in hypertensive nephropathy by inhibiting fibrosis and inflammation

This study intends to investigate the correlation between hypertensive nephropathy (HN) and microRNA-23b-3p (miR-23b-3p), and clarify the biological function of miR-23b-3p in renal injury.

The serum expression levels of miR-23b-3p were compared between HN patients and healthy controls. A mouse model of HN was constructed via persistent Ang II infusion, after which the effects of miR-23b-3p on renal function (ACR/Scr/BUN) were examined. The mRNA levels of renal fibrosis markers (TGF-β1, COL1A1, Fibronectin, α-SMA) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in kidney tissues were quantified by RT-qPCR. For in vitro validation, NRK-52E cells were stimulated with Ang II. The interaction between miR-23b-3p and phosphodiesterase 4B (PDE4B) was verified using dual luciferase reporter assay and RNA pull-down assay.

In patients with HN, the expression level of miR-23b-3p was positively correlated with eGFR and negatively correlated with ACR. In the mouse model, inhibition of miR-23b-3p exacerbated renal injury; conversely, overexpression of miR-23b-3p exerted a protective effect, which was specifically manifested as decreased levels of ACR, Scr, BUN, fibrotic factors and pro-inflammatory factors. PDE4B is a downstream target gene of miR-23b-3p. The expression trend of PDE4B was opposite to that of miR-23b-3p in HN patients, Ang II-induced mouse models and NRK-52E cells. In NRK-52E cells, PDE4B attenuated the inhibitory effect of miR-23b-3p on fibrotic genes and inflammatory genes.

The pathogenesis of HN is closely associated with the aberrant expression of miR-23b-3p. miR-23b-3p may ameliorate renal tubular fibrosis and inflammatory response via negatively regulating its target gene PDE4B.