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Inflammation
Published in: Inflammation 4/2019

Open Access 01-08-2019 | Kidney Injury | ORIGINAL ARTICLE

Fractalkine is Involved in Lipopolysaccharide-Induced Podocyte Injury through the Wnt/β-Catenin Pathway in an Acute Kidney Injury Mouse Model

Authors: Soulixay Senouthai, Junjie Wang, Dongdong Fu, Yanwu You

Published in: Inflammation | Issue 4/2019

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Abstract

Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases as well as being associated with the progression of kidney disease. Activation of the Wnt/β-catenin pathway is associated with the pathogenesis of podocyte dysfunction and can play a role in renal injury. Furthermore, the expression of fractalkine (FKN) induced by lipopolysaccharides (LPS) is also one of crucial inflammation factors closely related to renal tissue damage. The aim of this study is to explore the mechanism of LPS-induced FKN expression leading to podocyte injury and contribute to acute kidney injury (AKI) through regulation of Wnt/β-catenin pathway. An AKI model was established for in vivo experiments and blood was collected for serum BUN and Cr measurement, and histopathological features of the kidneys were studied by PASM and IHC staining. For in vitro experiments, a mouse podocyte cell line was stimulated with different concentrations of LPS for 24 and 48 h after which podocyte viability and apoptosis of cells were evaluated. The expression of podocyte-specific markers, FKN and Wnt/β-catenin pathway mRNA and protein was detected in mice and cells by using qRT-PCR and western blotting. LPS induced the expression of FKN and activation of the Wnt/β-catenin pathway, leading to a decrease of podocyte-specific proteins which resulted in poor renal pathology and dysfunction in the AKI mouse model. Moreover, LPS treatment significantly decreased cell viability and induced podocyte apoptosis in a dose-dependent manner that causes changes in the expression of podocyte-specific proteins through activation of FKN and the Wnt/β-catenin pathway. Thus, the expression of FKN and Wnt/β-catenin pathway by LPS is closely associated with podocyte damage or loss and could therefore account for progressive AKI. Our findings indicate that LPS induce podocyte injury and contribute to the pathogenesis of AKI by upregulating the expression of FKN and Wnt/β-catenin pathway.
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Metadata
Title
Fractalkine is Involved in Lipopolysaccharide-Induced Podocyte Injury through the Wnt/β-Catenin Pathway in an Acute Kidney Injury Mouse Model
Authors
Soulixay Senouthai
Junjie Wang
Dongdong Fu
Yanwu You
Publication date
01-08-2019
Publisher
Springer US
Published in
Inflammation / Issue 4/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-019-00988-1

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