Abstract
OBJECTIVE: This study investigated the therapeutic effects and mechanisms of IL-17A neutralisation on renal interstitial fibrosis and inflammation in spontaneously hypertensive rats (SHRs). METHODS: SHRs were treated with an IL-17A-neutralising antibody (NAb) for 20 weeks. Blood pressure and renal function were monitored. Renal tissues were analysed for histopathology, macrophage polarisation, epithelial-mesenchymal transition (EMT), inflammatory cytokines, and relevant signalling pathways. RESULTS: IL-17A NAb treatment significantly attenuated hypertension progression and improved renal function. It also ameliorated renal fibrosis and histopathological damage. Mechanistically, IL-17A neutralisation suppressed M2 macrophage polarisation and downregulated the TGF-β/Smad pathway, an effect associated with attenuated extracellular matrix (ECM) remodelling. This was accompanied by reduced levels of pro-inflammatory cytokines and inhibition of key inflammatory signalling pathways, including JAK/STAT, PI3K/AKT, and NF-κB. CONCLUSION: Our findings demonstrate that IL-17A neutralisation alleviates renal fibrosis and inflammation in SHRs. The protective effects are associated with the inhibition of M2 macrophage polarisation, suppression of the TGF-β/Smad pathway and the associated EMT process, and attenuation of systemic and renal inflammation, concomitant with the coordinated downregulation of the JAK/STAT, PI3K/AKT, and NF-κB signalling pathways.