title: High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells.
abstract: While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China; Department of Internal Medicine, Nan'an District People's Hospital, Chongqing 400060, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, The Fifth People's Hospital of Chongqing, Chongqing 400062, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Shishi
authors.initials: S
authors.lastname: Lü
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D018797:Cell Cycle Proteins; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000097:blood*; D011897:Random Allocation; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D017382:Reactive Oxygen Species; C493796:TXNIP protein, rat; D020170:Caspase 1; D005947:Glucose; D000111:Acetylcysteine