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Lipoxin A4 may attenuate the progression of obesity-related glomerulopathy by inhibiting NF-κB and ERK/p38 MAPK-dependent inflammation.

Abstract：

OBJECTIVES:To investigate the effects of lipoxin A4 (LXA4) on inflammatory responses in obesity-related glomerulopathy (ORG) mouse model and its potential mechanisms. METHODS:Male C57BL/6 mice were randomly divided into 4 groups: normal, model, LXA4, and LXA4/Boc-2 groups (n = 8). Mice in LXA4 group were intraperitoneally injected with LXA4 (40 ng/kg) once daily for 3 days following 12 weeks of high-fat diet (HFD) feeding. LXA4 receptor antagonist, Boc-2, was administered in LXA4/Boc-2 group prior to LXA4 treatment to block the effects of LXA4. Renal morphology and function impairment were determined. Inflammation was tested by measuring serum and mRNA levels of pro-inflammatory cytokines and chemokines. HFD-induced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of mitogen-activated protein kinases (MAPKs) were investigated by immunohistochemistry and western blot. RESULTS:HFD-feeding caused significant renal injury, pathological changes and inflammation in model group mice. LXA4 injection significantly alleviated HFD-induced effects on renal morphology and functions, as demonstrated by lower kidney index, glomerular diameter, 24 h urine protein, urinary albumin creatinine ratio and renal histomorphology. Moreover, HFD-induced accumulation of pro-inflammatory cytokines and chemokines were obviously attenuated by LXA4 administration, so did the HFD-induced activation of NF-κB and ERK/p38 MAPK pathways. However, these effects were markedly abrogated by BOC-2 pretreatment. CONCLUSION:LXA4 significantly attenuated HFD-induced renal inflammation and injury in ORG models, and these effects may be associated with the inhibition of activation of NF-κB and ERK/p38 MAPK pathways. The findings of our study may shed light on LXA4 showed a potential therapeutic application in ORG.

journal_name

Life Sci

journal_title

Life sciences

authors

Guo YP,Jiang HK,Jiang H,Tian HY,Li L

doi

10.1016/j.lfs.2018.02.039

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

112-118

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(18)30095-X

journal_volume

198

pub_type

杂志文章

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Lipoxin A4 may attenuate the progression of obesity-related glomerulopathy by inhibiting NF-κB and ERK/p38 MAPK-dependent inflammation.