Sodium butyrate regulation of NLRP3-Ser295 phosphorylation inhibits hypertensive nephropathy

Butyrate is a short-chain fatty acid with various pharmacological effects, which was produced by intestinal flora metabolism, we investigated the role and potential mechanism of sodium butyrate (NaBu) in angiotensin II (Ang II)-induced hypertensive kidney injury. A microosmotic pump containing Ang II was implanted into SD rats, and NaBu was injected intramuscularly from the third day of implantation for 28 days. We found that NaBu reduced the expression of Ang II-induced NLRP3 inflammasome-related proteins expression to mitigate NF-κB/IL-1β-mediated inflammation and pyroptosis mediated by gasdermin D (GSDMD) upregulation. Furthermore, NaBu repaired autophagy dysfunction due to lysosomal damage in macrophages. More importantly, we found that NaBu positively regulates Ser295 phosphorylation to modify NLRP3. Based on these results, we inferred that NaBu targets NLRP3 inflammasome degradation by regulating the p-NLRP3 (Ser295) to inhibit excessive pyroptosis, promoting the recovery of normal autophagy levels, thus indirectly affecting pyroptosis and ultimately improving hypertensive nephropathy.