TLR9 regulates NLRP3 inflammasome activation via the NF-kB signaling pathway in diabetic nephropathy

Background Toll-like receptors (TLRs) are critical sensors for the conservation of bacterial molecules and play a key role in host defense against pathogens. The effect of TLRs on the maintenance of diabetic nephropathy (DN) and resistance to infection has been investigated; however, the detailed effects of TLR9 on DN development remain elusive. Methods We performed quantitative reverse transcription-polymerase chain reaction and western blotting to detect TLR9 expression levels in the kidneys of experimental mice (db/db) and high-glucose-treated mouse mesangial cell strains (MCs). Results TLR9 expression was found to be remarkably upregulated in the kidneys of experimental mice (db/db) and MCs cultivated under hyperglycemic conditions. Moreover, knockdown of TLR9 could restrain NF-kB viability and downregulate the NLRP3 inflammasome in high glucose-treated MCs. TLR9 inhibition also alleviated inflammation and apoptosis, which was reversed by the addition of the NF-kappa B activator, betulinic acid. Furthermore, depleted TLR9 levels restrained NF-kappa B viability and NLRP3 expression and reduced kidney inflammation, microalbuminuria discharge, blood sugar level, and glomerular damage in experimental mice (db/db) kidneys. Conclusions These findings offer novel insights into the regulation of TLR9 via the nuclear factor-kB/NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome inflammation pathways in DN progression.