XAV939, a Wnt/β-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response

Jang, Jaewoong; Jung, Yoonju; Chae, Seyeon; Bae, Taehyun; Kim, Seok-Min; Shim, Yae Jie; Chung, Sunyang; Yoon, Yoosik

doi:10.1080/08923973.2018.1536984

Cited by 21 publications

(10 citation statements)

References 24 publications

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“…The XAV939 NPs group showed the lowest levels of IL-1β ( p < 0.01 vs. control and p < 0.01 vs. XAV939), IL-6 ( p < 0.01 vs. control and p < 0.05 vs. XAV939), and IL-17α ( p < 0.01 vs. control and p < 0.05 vs. XAV939). Our results are in accord with those obtained in a previous study that identified the anti-inflammatory activity of XAV939 in both human bronchial epithelial cells and HUVECs ( Jang et al, 2019 ). During the inflammatory process, the Wnt signaling pathway was activated, and XAV939 was found to dose-dependently suppress LPS-induced pro-inflammatory signaling ( Koopmans et al, 2017 ).…”

Section: Resultssupporting

confidence: 93%

Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization

Zhong

Wang

Zhang

et al. 2021

Front. Bioeng. Biotechnol.

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Corneal wound involves a series of complex and coordinated physiological processes, leading to persistent epithelial defects and opacification. An obstacle in the treatment of ocular diseases is poor drug delivery and maintenance. In this study, we constructed a Wnt/β-catenin pathway inhibitor, XAV939-loaded liposome (XAV939 NPs), and revealed its anti-inflammatory and antiangiogenic effects. The XAV939 NPs possessed excellent biocompatibility in corneal epithelial cells and mouse corneas. In vitro corneal wound healing assays demonstrated their antiangiogenic effect, and LPS-induced expressions of pro-inflammatory genes of IL-1β, IL-6, and IL-17α were significantly suppressed by XAV939 NPs. In addition, the XAV939 NPs significantly ameliorated alkali-burned corneas with slight corneal opacity, reduced neovascularization, and faster recovery, which were attributed to the decreased gene expressions of angiogenic and inflammatory cytokines. The findings supported the potential of XAV939 NPs in ameliorating corneal wound and suppressing neovascularization, providing evidence for their clinical application in ocular vascular diseases.

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Section: Resultssupporting

confidence: 93%

Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization

Zhong

Wang

Zhang

et al. 2021

Front. Bioeng. Biotechnol.

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“…Finally, to identify the role of the Wnt pathway in TCF7L1‐mediated damage protection against PRCs, the Wnt pathway inhibitor XAV939 was introduced into PRCs to block this pathway 26 . The Western blot data revealed that TCF7L1 expression was reduced while the Wnt pathway was activated in the PRCs exposed to blue light radiation.…”

Section: Resultsmentioning

confidence: 99%

Protective mechanism of TCF7L1 against retinal photoreceptor cell injury following retinitis pigmentosa based on the GEO database

Yin

Niu

et al. 2023

The FASEB Journal

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Recent studies have reported the promising value of differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) for identifying disease biomarkers. Based on this method, this study intends to characterize the hub genes and pathways related to retinal photoreceptor cell (PRC) injury in the context of retinitis pigmentosa (RP). A total of 53 coexpression modules were identified by WGCNA, among which lightpink4, darkolivegreen, tan4, blue2, skyblue2, and navajowhite2 ranked at the top. By analyzing the RP microarrays retrieved from the GEO database, 338 differentially expressed genes (DEGs) were identified in the RP samples. Forty-five candidate genes were selected from these DEGs by intersection with the genes in the coexpression modules. These intersection genes were subjected to GO and KEGG analyses. Furthermore, the genes and pathways involved in PRC damage were identified based on analyses utilizing GeneCards and STRING tools. Transcription factor 7-like 1 (TCF7L1, also called TCF3) was suggested to participate in the RP-associated PRC damage through the Wnt signaling pathway. It was validated in a blue light-irradiated cell model that TCF7L1 overexpression boosted PRC viability and repressed apoptosis. Inhibition of the Wnt signaling pathway also contributed to protective effects. Together, the data mentioned above supported the conclusion that either elevation of TCF7L1 or blockade of the Wnt signaling pathway could prevent RP progression by protecting PRCs from damage.

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“…Since some WNT ligands also exhibit pro-angiogenic activity in cancers, atherosclerosis, and eye diseases (Foulquier et al, 2018; Taciak et al, 2018; Wang et al, 2019), we hypothesized that WNT ligands secreted from placental villi could promote angiogenesis. To test this possibility, we used the β-catenin/CBP inhibitor ICG-001 (Akcora et al, 2018), as well as the tankyrase inhibitor XAV-939 (Jang et al, 2019), in combination with the conditioned media from IP, AEP, and REP, to interrogate the role of WNT signaling in angiogenesis using sprouting assay. Treatment with ICG-001 or XAV-939 significantly abolished the pro-angiogenic effects of conditioned media from IP or REP, suggesting that the angiogenic effects on HUVECs were canonical WNT signaling-dependent (Figure 4B and S4A).…”

Section: Resultsmentioning

confidence: 99%

Trophoblast and blood vessel organoid cultures recapitulate the role of WNT2B in promoting intravillous vascularization in human intrauterine and ectopic pregnancy

Zhao

Zhang

Luo

et al. 2022

Preprint

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SummaryTubal ectopic pregnancy (TEP), a pregnancy complication caused by aberrant implantation in fallopian tubes, accounts for 9-13% pregnancy-related deaths. The lack of models for human TEP hampers the understanding of its pathological mechanisms. Here, we employed multiple models to investigate the crosstalk between human trophoblast development and intravillous vascularization. We found that the severity of TEP, the size of placental villi, and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion. In an organoid coculture model consisting of trophoblast organoids and blood vessel organoids, knockdown of WNT2B in trophoblast organoids compromises their pro-angiogenic effect on the development of blood vessel organoids. These organoid-based models reveal an important role for WNT-mediated angiogenesis in pregnancies and could be employed to investigate the commutations between trophoblasts and endothelial/endothelial progenitor cells.

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XAV939, a Wnt/β-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response

Cited by 21 publications

References 24 publications

Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization

Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization

Protective mechanism of TCF7L1 against retinal photoreceptor cell injury following retinitis pigmentosa based on the GEO database

Trophoblast and blood vessel organoid cultures recapitulate the role of WNT2B in promoting intravillous vascularization in human intrauterine and ectopic pregnancy

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