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.
引用
收藏
页数:17
相关论文
共 50 条
  • [31] Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome
    Su, Bofeng
    Ye, Hong
    You, Xiaohan
    Ni, Haizhen
    Chen, Xuduan
    Li, Linlin
    LIFE SCIENCES, 2018, 208 : 26 - 32
  • [32] Linarin attenuates oxaliplatin-induced neuropathic pain by inhibiting NF-κB/NLRP3 signaling pathway
    Zeng, Siyu
    Ling, Chenming
    Chen, Hao
    Wang, Yu
    TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH, 2023, 22 (09) : 1797 - 1803
  • [33] Bortezomib inhibits NLRP3 inflammasome activation and NF-ΚB pathway to reduce psoriatic inflammation
    Chen, Xiuhui
    Chen, Yanhong
    Ou, Yitao
    Min, Wenjie
    Liang, Shuli
    Hua, Lei
    Zhou, Yinghua
    Zhang, Cheng
    Chen, Peifeng
    Yang, Zhongjin
    Hu, Wenhui
    Sun, Ping
    BIOCHEMICAL PHARMACOLOGY, 2022, 206
  • [34] Artemisinin alleviates atherosclerotic lesion by reducing macrophage inflammation via regulation of AMPK/NF-κB/NLRP3 inflammasomes pathway
    Jiang, Yan
    Du, Hongjiao
    Liu, Xue
    Fu, Xi
    Li, Xiaodong
    Cao, Qian
    JOURNAL OF DRUG TARGETING, 2020, 28 (01) : 70 - 79
  • [35] Canagliflozin Ameliorates NLRP3 Inflammasome-Mediated Inflammation Through Inhibiting NF-κB Signaling and Upregulating Bif-1
    Niu, Yaoyun
    Zhang, Yuehui
    Zhang, Wanqiu
    Lu, Jinghua
    Chen, Yang
    Hao, Wenhui
    Zhou, Jin
    Wang, Lijun
    Xie, Weidong
    FRONTIERS IN PHARMACOLOGY, 2022, 13
  • [36] Coptidis Rhizoma inhibits NLRP3 inflammasome activation and alleviates renal damage in early obesity-related glomerulopathy
    Ren Yanlin
    Wang Dingkun
    Lu Fuer
    Zou Xin
    Xu Lijun
    Wang Kaifu
    Huang Wenya
    Su Hao
    Zhang Chu
    Gao Yang
    Dong Hui
    PHYTOMEDICINE, 2018, 49 : 52 - 65
  • [37] Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF-κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy
    Wen, Yi
    Pan, Ming-Ming
    Lv, Lin-Li
    Tang, Tao-Tao
    Zhou, Le-Ting
    Wang, Bin
    Liu, Hong
    Wang, Feng-Mei
    Ma, Kun-Ling
    Tang, Ri-Ning
    Liu, Bi-Cheng
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (03) : 4291 - 4300
  • [38] Downregulation of FSTL-1 attenuates the inflammation injury during Streptococcus pneumoniae infection by inhibiting the NLRP3 and TLR4/NF-κB signaling pathway
    Chen, Liang
    Liu, Zhenshe
    MOLECULAR MEDICINE REPORTS, 2019, 20 (06) : 5345 - 5352
  • [39] Tectoridin alleviates lipopolysaccharide-induced inflammation via inhibiting TLR4-NF-κB/NLRP3 signaling in vivo and in vitro
    Niu, Xiaofeng
    Song, Huixin
    Xiao, Xin
    Yu, Jinjin
    Yu, Jiabao
    Yang, Yajie
    Huang, Qiuxia
    Zang, Lulu
    Han, Tengfei
    Zhang, Dezhu
    Li, Weifeng
    IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, 2022, 44 (05) : 641 - 655
  • [40] Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota
    Ding, Ming-Hui
    Xu, Peng-Gang
    Wang, Ying
    Ren, Bao-di
    Zhang, Jun-Li
    IMMUNOLOGICAL INVESTIGATIONS, 2023, 52 (02) : 194 - 209