Format

Send to

Choose Destination
Inflammation. 2017 Oct;40(5):1707-1716. doi: 10.1007/s10753-017-0612-7.

Lysophosphatidic Acid Protects Against Endotoxin-Induced Acute Kidney Injury.

Author information

1
U1048, Institut of Cardiovascular and Metabolic Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
2
Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France.
3
Centre de Microscopie Electronique Appliquée à la Biologie (CMEAB), Faculté de Médecine Rangueil, University of Toulouse, Toulouse, France.
4
U1188-Université de La Réunion, Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
5
U1048, Institut of Cardiovascular and Metabolic Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France. joost-peter.schanstra@inserm.fr.
6
Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France. joost-peter.schanstra@inserm.fr.
7
U1048, Institut of Cardiovascular and Metabolic Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France. jean-sebastien.saulnier-blache@inserm.fr.
8
Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France. jean-sebastien.saulnier-blache@inserm.fr.

Abstract

Septic shock is the most common cause of acute kidney injury (AKI), but the underlying mechanisms remain unclear and no targeted therapies exist. Lysophosphatidic acid (LPA) is a bioactive lipid which in vivo administration was reported to mitigate inflammation and injuries caused by bacterial endotoxemia in the liver and lung. The objective of the present study was to determine whether LPA can protect against sepsis-associated AKI. C57BL/6 mice were treated with LPA 18:1 (5 mg/kg, i.p.) 1 h before being injected with the endotoxin lipopolysaccharide (LPS), and AKI was evaluated after 24 h. LPA significantly decreased the elevation of plasma urea and creatinine caused by LPS. In the kidney, LPA pretreatment significantly reduced the upregulation of inflammatory cytokines (IL-6, TNFα, monocyte chemoattractant protein-1 (MCP-1)), and completely prevented downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and upregulation of heme oxygenase-1 caused by LPS. LPA also prevented LPS-mediated alterations of the renal mitochondrial ultrastructure. In vitro pretreatment with LPA 18:1 significantly attenuated LPS-induced upregulation of the inflammatory cytokines (TNFα and MCP-1) in RAW264 macrophages. Moreover, in vivo LPS treatment lowered urinary LPA concentration and reduced LPA anabolic enzymes (autotaxin and acylglycerol kinase), and increased the LPA catalytic enzyme (lipid phosphate phosphatase 2) expression in the kidney cortex. In conclusion, exogenous LPA exerted a protective action against renal inflammation and injuries caused by bacterial endotoxemia. Moreover, LPS reduces the renal production of LPA suggesting that sepsis-associated AKI could be mediated, at least in part, by alleviation of the protective action of endogenous LPA.

KEYWORDS:

endotoxemia; kidney; lysophosphatidic acid; macrophages

PMID:
28667502
DOI:
10.1007/s10753-017-0612-7
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center