MicroRNA-155 Mediates Obesity-Induced Renal Inflammation and Dysfunction

被引:25
作者
Zheng, Chenfei [1 ]
Zhang, Ji [1 ]
Chen, Xinxin [1 ]
Zhang, Jianna [1 ]
Ding, Xiaokai [1 ]
You, Xiaohan [1 ]
Fan, Lin [1 ]
Chen, Chaosheng [1 ]
Zhou, Ying [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Nephrol, Wenzhou 325000, Peoples R China
关键词
obesity; nephropathy; miR-155; inflammation; SHIP1; INPP5D; MYCOPHENOLATE-MOFETIL; DIABETIC-NEPHROPATHY; INSULIN-RESISTANCE; MIR-155; STRESS; TARGET; STAGE;
D O I
10.1007/s10753-019-00961-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chronic inflammation is a major contributor to obesity-related renal damage. Recent studies have demonstrated that microRNA (miR)-155 is closely associated with hyperglycemia-induced nephropathy, but whether renal miR-155 participates in the inflammatory response and development of obesity-related nephropathy is unknown. In present study, we investigated the pathophysiological role of renal miR-155 in palmitic acid (PA)-treated endothelial cell and high-fat-diet (HFD)-fed mouse models by specific miR-155 sponge. Mice fed with HFD exhibited higher levels of renal miR-155, which positively correlated with urine microalbumin and blood urea nitrogen. In vitro study, mouse renal vascular endothelial cells stimulated with PA also showed higher miR-155 levels, accompanied with increased inflammatory response. Suppression of renal miR-155 effectively attenuated HFD-induced renal structural damages and dysfunction. MiR-155 sponge treatment also significantly decreased NF-B signaling and downstream gene expression in vitro and in vivo. The obesity-increased macrophage infiltration and lipotoxicity was decreased in mouse kidney after miR-155 sponge treatment. Mechanistically, miR-155 directly targeted 3-UTR of SHIP1/INPP5D and suppressed its expression in vitro and in vivo, whereas silence of SHIP1/INPP5D abolished the renal protective benefits of miR-155 sponge in obese mice. Taken together, present findings for the first time provided evidence for the potential role of miR-155 in obesity-related nephropathy and clarified that SHIP1/NF-B signaling was a potential molecular mechanism.
引用
收藏
页码:994 / 1003
页数:10
相关论文
共 35 条
  • [1] Src homology 2 domain-containing inositol-5-phosphatase 1 (SITP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism
    An, HZ
    Xu, HM
    Zhang, MH
    Zhou, J
    Feng, T
    Qian, C
    Qi, RZ
    Cao, XT
    [J]. BLOOD, 2005, 105 (12) : 4685 - 4692
  • [2] Macrophage-derived tumor necrosis factor-α mediates diabetic renal injury
    Awad, Alaa S.
    You, Hanning
    Gao, Ting
    Cooper, Timothy K.
    Nedospasov, Sergei A.
    Vacher, Jean
    Wilkinson, Patrick F.
    Farrell, Francis X.
    Reeves, W. Brian
    [J]. KIDNEY INTERNATIONAL, 2015, 88 (04) : 722 - 733
  • [3] NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules
    Baeuerle, PA
    Baichwal, VR
    [J]. ADVANCES IN IMMUNOLOGY, VOL 65, 1997, 65 : 111 - 137
  • [4] Pathophysiology of Obesity-Related Renal Dysfunction Contributes to Diabetic Nephropathy
    Bayliss, George
    Weinrauch, Larry A.
    D'Elia, John A.
    [J]. CURRENT DIABETES REPORTS, 2012, 12 (04) : 440 - 446
  • [5] The Inositol Phosphatase SHIP-1 Inhibits NOD2-Induced NF-κB Activation by Disturbing the Interaction of XIAP with RIP2
    Conde, Claude
    Rambout, Xavier
    Lebrun, Marielle
    Lecat, Aurore
    Di Valentin, Emmanuel
    Dequiedt, Franck
    Piette, Jacques
    Gloire, Geoffrey
    Legrand, Sylvie
    [J]. PLOS ONE, 2012, 7 (07):
  • [6] Inflammation, free radicals, and antioxidants
    Conner, EM
    Grisham, MB
    [J]. NUTRITION, 1996, 12 (04) : 274 - 277
  • [7] Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease
    de Vries, Aiko P. J.
    Ruggenenti, Piero
    Ruan, Xiong Z.
    Praga, Manuel
    Cruzado, Josep M.
    Bajema, Ingeborg M.
    D'Agati, Vivette D.
    Lamb, Hildo J.
    Barlovic, Drazenka Pongrac
    Hojs, Radovan
    Abbate, Manuela
    Rodriquez, Rosa
    Mogensen, Carl Erik
    Porrini, Esteban
    [J]. LANCET DIABETES & ENDOCRINOLOGY, 2014, 2 (05) : 417 - 426
  • [8] Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy
    Elmarakby, Ahmed A.
    Sullivan, Jennifer C.
    [J]. CARDIOVASCULAR THERAPEUTICS, 2012, 30 (01) : 49 - 59
  • [9] Inflammation, Oxidative Stress, and Obesity
    Fernandez-Sanchez, Alba
    Madrigal-Santillan, Eduardo
    Bautista, Mirandeli
    Esquivel-Soto, Jaime
    Morales-Gonzalez, Angel
    Esquivel-Chirino, Cesar
    Durante-Montiel, Irene
    Sanchez-Rivera, Graciela
    Valadez-Vega, Carmen
    Morales-Gonzalez, Jose A.
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2011, 12 (05) : 3117 - 3132
  • [10] Obesity, metabolic syndrome, and cardiovascular disease
    Grundy, SM
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (06) : 2595 - 2600