Title:The Selective NLRP3-Inflammasome Inhibitor CY-09 Ameliorates
Kidney Injury in Diabetic Nephropathy by Inhibiting NLRP3-
inflammasome Activation
Volume: 30
Issue: 28
Author(s): Ming Yang and Li Zhao*
Affiliation:
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University,
Kunming, China
Keywords:
NLRP3 inflammasome, CY-09, DN, inflammation, renal pathology, hyperglycemia.
Abstract:
Background: Diabetic nephropathy (DN) is one of the most serious complications
of diabetes mellitus and the main cause of the end-stage renal disease (ESRD). Activation
of the NLRP3 inflammasome has been proven to play an important role in the development
of DN. Thus, specific and direct targets of NLRP3 inflammasome assembly
may have therapeutic potential. CY-09 is a new NLRP3 inflammasome specific inhibitor
that has been shown to protect against non-alcoholic fatty liver disease (NAFLD) by inhibiting
the activation of the NLRP3 inflammasome. However, its role in kidney disease,
especially DN, has not been reported.
Methods: In this study, we used HE staining to assess renal pathological damage in each
group, and RT-PCR, immunofluorescence and WB were performed to detect the expression
changes in inflammatory and fibrosis proteins. The apoptosis level was detected by
TUNEL staining.
Results: Here, we showed increased inflammation, oxidative stress, apoptosis and fibrosis
in db/db mice, while CY-09 exerted renoprotection by inhibiting NLRP3 inflammasome
activation. In vitro, CY-09 also inhibited NLRP3 and reduced caspase-1, IL-18, IL-1β and
apoptosis in a dose-dependent manner.
Conclusion: CY-09 effectively protects the kidney from hyperglycemia induced damage
by inhibiting the NLRP3 inflammasome and may be a promising therapeutic strategy to
prevent the progression of DKD.
