Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN. Methods: DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and M...

Full description

Saved in:
Bibliographic Details
Published in:Renal failure Vol. 45; no. 1; p. 2165103
Main Authors: Lv, Chenlei, Cheng, Tianyang, Zhang, Bingbing, Sun, Ke, Lu, Keda
Format: Journal Article
Language:English
Published: England Taylor & Francis 01.12.2023
Taylor & Francis Ltd
Taylor & Francis Group
Subjects:
Animal models
Animals
Apoptosis
Body weight
Cell viability
Clinical Study
Creatinine
Diabetes
Diabetes Mellitus
Diabetic Nephropathies - drug therapy
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - prevention & control
Diabetic nephropathy
Heme oxygenase (decyclizing)
Heme Oxygenase-1 - metabolism
High fat diet
Inflammasomes
Inflammasomes - metabolism
Inflammasomes - pharmacology
Inflammation
Mice
Microvasculature
MPC5
Nephropathy
NF-E2-Related Factor 2 - metabolism
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
NLRP3 inflammasome
Nrf2
Oxidative stress
Podocytes - pathology
Pyrin protein
Pyroptosis
Reactive oxygen species
Reactive Oxygen Species - metabolism
Renal function
Streptozocin
Triptolide
Western blotting
MPC5
Diabetic nephropathy
triptolide
NLRP3 inflammasome
Nrf2
oxidative stress
ISSN:0886-022X, 1525-6049, 1525-6049
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN. Methods: DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2. Results: TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells. Conclusions: Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors contributed equally to this work.
ISSN:0886-022X
1525-6049
1525-6049
DOI:10.1080/0886022X.2023.2165103