Rehmannioside A alleviates renal inflammation and fibrosis in hypertensive nephropathy via AT1R/MAPK14/IL-17 signaling pathway

Background

This study aimed to observe the influences and potential mechanism of rehmannioside A (ReA) in hypertensive nephropathy (HN).

Methods

HN model in mice and rat tubular epithelial cells were constructed by angiotensin II (Ang II). The biomarkers of renal function, including uric acid (UA), creatinine (Cre), blood urea nitrogen (BUN), and urine albumin, were assessed.

Results

Ang II induced severe kidney injury, while the injury was ameliorated by ReA. In Ang II-induced hypertensive mice model, ReA decreased the levels of UA, Cre, BUN, urine albumin, transforming growth factor (TGF)-β, Fibronectin, Collagen I, interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-α. In Ang II-treated cells, ReA reduced the levels of TGF-β, Fibronectin, Col1agen I, IL-6, IL-1β, and TNF-α. In vivo and in vitro, ReA promoted angiotensin converting enzyme 2 (ACE2) expression and inhibited the expression of angiotensin II type 1 receptor (AT1R), ACE, IL-17, mitogen activated protein kinase 14 (MAPK14), phosphorylated (p)-MAPK14, p–NF–κB P65, and matrix metallopeptidase 9 (MMP-9) in HN model. Moreover, there was a docking for ReA and MAPK14 protein, and ReA inhibited MAPK14 protein expression by promoting MAPK14 ubiquitination. Under Ang II treatment, MAPK14 overexpression reversed the promotive effect of ReA on cell viability and the inhibitory effects of ReA on fibrosis and inflammation in NRK-52E cells.

Conclusions

ReA alleviated renal dysfunction and reduced fibrosis and inflammation, which was related to the inhibition of AT1R/MAPK14/IL-17 pathway. For HN treatment, ReA may be a promising pharmacological strategy.