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.

Automated summary

The study reveals the significant role of TLR9 in the development of diabetic nephropathy. Inhibition of TLR9 can alleviate inflammation and apoptosis, and improve kidney function. These findings provide new insights for the treatment of DN.