Activation of Wnt signaling reduces high-glucose mediated damages on skin fibroblast cells

Wang, Youpei and Zheng, Xiang and Wang, Qing and Zheng, Meiqin and Pang, Lingxia (2017) Activation of Wnt signaling reduces high-glucose mediated damages on skin fibroblast cells. Iranian Journal of Basic Medical Sciences, 20 (8). pp. 944-950.

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Abstract

Objective(s): High-glucose (HG) stress, a mimic of diabetes mellitus (DM) in culture cells, alters expression of a large number of genes including Wnt and NF-κB signaling-related genes; however, the role of Wnt signaling during HG-mediated fibroblast damage and the relationship between Wnt and NF-κB signaling have not been understood. In this study, we aimed to investigate the ffects of Wnt signaling on HG-mediated damages. Materials and Methods: Wnt3a was treated to HG-stressed human primary foreskin fibroblasts and the levels of Wnt signaling markers and cell proliferation were monitored. In addition, Wnt3a and NF-κB signaling inhibitor were assisted to analyze the relationship between two pathways. Results: The results indicated that HG treatment repressed β-catenin level, and Wnt3a treatment increased the levels of β-catenin and FZD8 as well as cell proliferation. RNA-seq based transcriptome analysis identified 207 up-regulated and 200 down-regulated genes upon Wnt3a supply. These altered genes are distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicates that 20 GO terms are enriched. Wnt signaling genes were further verified by qRT-PCR and the results were similar with RNA-seq assay. Since NF-κB signaling negatively regulates Wnt marker gene expression, Bay117082, a typical NF-κB signaling inhibitor and Wnt3a were supplemented for testing β-catenin and phosphorylated IκBα (p-IκBα), respectively. Conclusion: HG positively inhibits Wnt signaling, and signaling activation via supplementation of Wnt3a rescued the defect caused by HG. NF-κB signaling negatively regulates accumulation of β-catenin, but Wnt signaling has no effects on IκBα activation.

Item Type: Article
Subjects: QU Biochemistry
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 04 Sep 2017 17:01
Last Modified: 04 Sep 2017 17:01
URI: http://eprints.mums.ac.ir/id/eprint/128

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