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Adiponectin protects obesity-related glomerulopathy by inhibiting ROS/NF-κB/NLRP3 inflammation pathway
被引:36
作者:
Xu, Xiaohong
[1
,2
,3
]
Huang, Xiaolin
[1
]
Zhang, Liexiang
[4
,5
]
Huang, Xiaoli
[1
]
Qin, Zihan
[1
]
Hua, Fei
[1
]
机构:
[1] Soochow Univ, Affiliated Hosp 3, Dept Endocrinol, 185 Bur Front St, Changzhou 213003, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Affiliated Suqian Hosp, Dept Nephrol, Suqian City, Peoples R China
[3] Nanjing Drum Tower Hosp Grp, Suqian Peoples Hosp, Dept Nephrol, Suqian City, Peoples R China
[4] Xuzhou Med Univ, Affiliated Suqian Hosp, Dept Neurosurg, Suqian City, Peoples R China
[5] Nanjing Drum Tower Hosp Grp, Suqian Peoples Hosp, Dept Neurosurg, Suqian City, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Adiponectin;
Obesity-related glomerulopathy;
ROS;
NF-kappa B;
NLRP3;
inflammation;
NLRP3;
INFLAMMASOME;
OXIDATIVE STRESS;
ACTIVATION;
PODOCYTES;
HOMEOSTASIS;
CLEARANCE;
RECEPTORS;
FIBROSIS;
SYSTEM;
ALPHA;
D O I:
10.1186/s12882-021-02391-1
中图分类号:
R5 [内科学];
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号:
1002 ;
100201 ;
摘要:
Background: Adiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG. Methods: Small-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot. Results: Podocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1 beta), and induced activation of NF-kappa B as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-kappa B in podocytes. Pyrrolidine dithiocarbamate, an NF-kappa B inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation. Conclusions: Our study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-kappa B/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.
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页数:17
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