Dataset Information

Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis.

ABSTRACT: The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4- or TGFβ1-induced processes. In a mouse model, induced deletion of β-catenin in macrophages attenuated the fibrosis, macrophage accumulation, and M2 polarization observed in the kidneys of wild-type littermates after unilateral ureter obstruction. This study shows that activation of Wnt/β-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.

SUBMITTER: Feng Y

PROVIDER: S-EPMC5748914 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis.

Feng Ye Y Ren Jiafa J Gui Yuan Y Wei Wei W Shu Bingyan B Lu Qingmiao Q Xue Xian X Sun Xiaoli X He Weichun W Yang Junwei J Dai Chunsun C

Journal of the American Society of Nephrology : JASN 20171011 1

The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGFβ1-induced macrophage alternative (M2) polarization and the phosp ...[more]

PMID: 29021383

Similar Datasets

Project description:BackgroundPre-eclampsia (PE) is a pregnancy specific disease characterized by hypertension and proteinuria. The aim of this study was to investigate the effects of Zinc finger E-box binding homologous box 2 (ZEB2) on PE mice and on placental trophoblast cells, as well as to elucidate its role in Wnt/β-Catenin pathway.MethodsThe PE mice models were established through L-NAME administration. RT-qPCR and western blot assay were used to detect the expression of ZEB2 in human serum, placental tissues, HTR8/Sveno cells, and mice models. Edu assay, flow cytometry, and Transwell analysis were applied for determining HTR8/Sveno cells proliferation, apoptosis, migration, and invasion ability, respectively. The expression levels of related proteins in the Wnt/β-Catenin pathway were detected by western blot analysis. The systolic blood pressure (SBP) of mice was analyzed by the noninvasive tail cuff method. Proteinuria was detected using CBB kits and TUNEL method was used to measure apoptosis of placental tissue cells in PE mice.ResultsThe significant increase SBP and urinary protein in L-NAME treated mice indicated the successful construction of the PE mice model. We found that ZEB2 was down-regulated in the serum and placental tissues of PE patients. Further in vitro experiments showed that ZEB2-plasmid enhanced cell proliferation, migration, and invasion, as well as reduced cell apoptosis, compared with the control-plasmid group. In addition, up-regulation of ZEB2 promoted the protein level of Bcl-2 in HTR-8/SVneo cells and inhibited Bax expression. We also found that ZEB2-plasmid activated Wnt/β-Catenin signaling pathway, as confirmed by enhanced Wnt3a, β-Catenin, p-GSK3β, C-Myc, and Cyclin D1 expression. Importantly, the Wnt/β-Catenin signaling inhibitor (XAV939) partially reversed the effects of ZEB2-plasmid on HTR-8/SVneo cells. We also observed similar findings in in vivo mice models as in vitro cell experiments.ConclusionZEB2 was involved in the pathological and physiological processes of PE through Wnt/β-Catenin pathway, which may provide a useful perspective for exploring new therapies for PE.

Dataset Information

Wnt/β-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis.

Publications

Wnt/<i>β</i>-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets