imprint:
Springer Science and Business Media LLC, 2022
Published in:Diabetology & Metabolic Syndrome
Language:
English
DOI:
10.1186/s13098-021-00780-y
ISSN:
1758-5996
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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).</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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-κB activator, betulinic acid. Furthermore, depleted TLR9 levels restrained NF-κB viability and NLRP3 expression and reduced kidney inflammation, microalbuminuria discharge, blood sugar level, and glomerular damage in experimental mice (db/db) kidneys. </jats:p>
<jats:p>Conclusions</jats:p>
<jats:p>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.</jats:p>
</jats:sec>