Esaxerenone attenuates renal injury by inhibiting NR3C2-mediated inflammatory and fibrotic pathways

Renal inflammation and fibrosis are pathological features of various types of kidney diseases. High-salt diet and aldosterone are risk factors for inducing kidney disease. Esaxerenone is the mineralocorticoid receptor blocker which is effective in treating hypertension. The aim of this study is to observe the effect of esaxerenone on renal inflammation in a rat model of high-salt diet plus aldosterone infusion. We found that rats treated with high-salt diet plus aldosterone showed more serious renal pathological injury. As well as, the expression of kidney injury molecule-1, toll-like receptor 4 (TLR4), phospho-nuclear factor kappa-B‌ (p-NF-κB), F4/80, interleukin-6, ‌tumor necrosis factor-alpha, and interferon gamma were increased (p < 0.05). In addition, high-salt diet plus aldosterone could upregulate the expression of transforming growth factor-beta‌ (TGF-β), p-Smad2, p-Smad3, alpha-smooth muscle actin, vimentin, and collagen I (p < 0.05). However, administration of esaxerenone could ameliorate high-salt diet plus aldosterone - induced these expressions and renal pathological injury (p < 0.05). These data suggest that esaxerenone may alleviate high-salt plus aldosterone-induced renal inflammation and fibrosis by regulating the TLR4/NF-κB and TGF-β/Smad signaling pathways.