WWOX and metabolic regulation in normal and pathological conditions

Baryła, Izabela; Kośla, Katarzyna

doi:10.1007/s00109-022-02265-5

Cited by 4 publications

(3 citation statements)

References 107 publications

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“…For FBs, the most obvious master regulators of the TF identified were WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN. WWOX (WW domain containing oxidoreductase) is involved in cell proliferation, differentiation, and metabolism [ 73 ]. Mutations in the WWOX gene cause neurodevelopmental and brain degenerative disorders [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress

et al. 2023

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Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory shear stress or left at the static condition. Then, other cell types were treated with preconditioned media from the adjacent layer’s cells. DNA isolated from the harvested cells was subjected to epigenome-wide study using Illumina microarrays followed by data analysis with GenomeStudio (Illumina), Excel (Microsoft), and Genome Enhancer (geneXplain) software packages. Differential (hypo-/hyper-) methylation was revealed for each cell layer’s DNA. The most targetable master regulators controlling the activity of certain transcription factors regulating the genes near the differentially methylated sites appeared to be the following: (1) HGS, PDGFB, and AR for endothelial cells; (2) HGS, CDH2, SPRY2, SMAD2, ZFYVE9, and P2RY1 for smooth muscle cells; and (3) WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN for fibroblasts. Some of the identified master regulators may serve as promising druggable targets for treating varicose veins in the future.

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Section: Discussionmentioning

confidence: 99%

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress

et al. 2023

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“…WWOX has been shown to play a crucial role not only in cancer development but also in various other cellular processes [ 18 ]. Several studies indicate WWOX involvement in high-density lipoprotein (HDL) cholesterol, triglyceride, and other lipoprotein metabolism [ 19 , 20 ]. Additionally, WWOX deficiency can lead to decreased mitochondrial oxidation, increased glycolysis, and fatty acid oxidation, ultimately contributing to the development of metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis

Shin,

Kim,

Lee

et al. 2023

IJMS

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Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

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“…WWOX participates in cell death, differentiation, signaling, and protein–protein interactions, as well as in cell migration and recognition [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Substantial evidence has shown that WWOX plays a critical role in limiting neurodegeneration such as AD and neuronal damage [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Loss of WWOX in newborns results in severe neural diseases, metabolic disorders, mental retardation, stunt growth, and early death [ 28 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration

Lin

Shih

Yap

et al. 2022

IJMS

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When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6AΔ (TPC6AΔ), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Aβ) generation, and neurodegeneration, as shown in Alzheimer’s disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6AΔ, along with aggregation of TIAF1, SH3GLB2, Aβ, and tau, occurred. MPP+ is an inducer of Parkinson’s disease (PD), suggesting that TPC6AΔ is a common initiator for AD and PD pathogenesis. Zfra, a 31-amino-acid zinc finger-like WWOX-binding protein, is known to restore memory deficits in 9-month-old triple-transgenic (3xTg) mice by blocking the aggregation of TPC6AΔ, SH3GLB2, tau, and amyloid β, as well as inflammatory NF-κB activation. The Zfra4-10 peptide exerted a strong potency in preventing memory loss during the aging of 3-month-old 3xTg mice up to 9 months, as determined by a novel object recognition task (ORT) and Morris water maize analysis. Compared to age-matched wild type mice, 11-month-old Wwox heterozygous mice exhibited memory loss, and this correlates with pT12-WWOX aggregation in the cortex. Together, aggregation of pT12-WWOX may link to TPC6AΔ aggregation for AD progression, with TPC6AΔ aggregation being a common initiator for AD and PD progression.

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WWOX and metabolic regulation in normal and pathological conditions

Cited by 4 publications

References 107 publications

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis

Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration

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