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Last update 08 May 2025

WIF1

Last update 08 May 2025

Basic Info

Synonyms

WIF-1, WIF1, WNT inhibitory factor 1

Introduction

Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.

Drugs associated with WIF1

HG-1427

Target

WIF1

Mechanism

WIF1 inhibitors

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with WIF1

100 Translational Medicine associated with WIF1

0 Patents (Medical) associated with WIF1

659

Literatures (Medical) associated with WIF1

02 Apr 2025·Science Translational Medicine

Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis

Article

Author: Chen, Xiaoying ; Niu, Jianqin ; Wu, Zhonghao ; Verkhratsky, Alexei ; Wang, Xiaorui ; Liu, Yang ; Huang, Taida ; Wang, Qi ; Yu, Guangdan ; Tian, Yi ; Yi, Chenju ; Zheng, Zihan ; Zeng, Cong ; Wan, Ying ; Li, Hui ; Su, Yixun ; Zhang, Jinyu ; Zhuang, Yuan ; Jiang, Zhuoxu ; Yang, Qingwu

Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelination and to developing early intervention strategies. Here, we aimed to model overactivated Wnt (wingless-related integration site) signaling previously shown in postmortem brain tissues of patients with MS by inducing experimental autoimmune encephalomyelitis (EAE) in Pdgfra CreER ;Apc fl/fl and Olig2 Cre ;Apc fl/fl mice. These mice have overactivated Wnt signaling in oligodendrocyte precursor cells (OPCs) because of a conditional knockout of the pathway repressor adenomatous polyposis coli (APC). Pdgfra CreER ;Apc fl/fl EAE mice exhibited increased expression of markers for Wnt activation such as Axis inhibition protein 2 (AXIN2) and Wnt inhibitory factor 1 (WIF1) in OPCs and showed exacerbated EAE progression in both the spinal cord and the brain. Genetic or antibody-mediated ablation of CC-chemokine ligand 4 (CCL4) prevented infiltration of CD4 + T cells and arrested disease progression in these mice. A characterization of CNS (central nervous system) immune cell clusters identified an augmented subpopulation of NK1.1 + CD11b + Gr-1 + cytotoxic macrophages in Pdgfra CreER ;Apc fl/fl EAE mice. Microinjection of this subpopulation of macrophages into the brains of wild-type C57/B6J mice was sufficient to induce demyelination. Ablation of CD4 + T cells prevented the effects of Wnt overactivation on demyelination and immune cell infiltration. Antagonizing chemokine receptor 5 (CCR5) using a European Medicines Agency–approved drug, maraviroc, reduced immune cell infiltration, alleviated demyelination, and attenuated EAE progression. We found an OPC-orchestrated immune cellular network that instigates early demyelination, provides insight into MS pathophysiology, and suggests avenues for early interventions.

01 Apr 2025·Journal of Cellular and Molecular Medicine

Kaempferol Targets Global Epigenetic Modifiers to Impedes Growth and Migratory Ability of HeLa Cells

Article

Author: Hussain, Arif ; Haque, Shafiul ; Afroze, Nazia

ABSTRACTDietary bioactive agents can curb tumour progression through chromatin alterations. Thus, this study attempts to evaluate the influence of kaempferol on epigenome modification in HeLa cells. Biochemical analysis for global DNA methylation‐LINE 1, DNMTs (DNA methyltransferases), HAT (histone acetyl transferase), HDACs (histone deacetylases) and HMTs (histone methyltransferases) were examined with their transcript level expression through qPCR. Also, H3 and H4 histone modification marks were quantitated by an ELISA‐based assay. Moreover, qPCR and protein profiler were performed to analyse the expression of migratory genes at both mRNA and protein levels, respectively, that was further substantiated through colony formation, invasion, and scratch wound assays. Finally, DNA methyl‐sequencing was performed to analyse the promoter methylation of TSGs (tumour suppressor genes) and corroborated by analysing selected TSGs' expression. Kaempferol treatment did not alter the global DNA methylation‐LINE 1 compared to untreated control, however, it reduced the expression and biochemical activities of DNMT and HDAC, which can be linked to their hypermethylation by kaempferol exposure. Concordant with the reduced expression of HMTs, HATs and other epi‐enzymes, various histone H3 and H4 marks were also observed to be modulated. Kaempferol exposure led to promoter hypomethylation of various TSGs (such as WIF1, RUNX1, RARβ, SOX1), which subsequently led to enhanced expression at the mRNA level, which corresponds to their reactivation. Molecular studies were consistent with cell‐based studies, which demonstrated a strong growth inhibitory and anti‐migratory effect of kaempferol. This research helps to understand the probable mechanism used by kaempferol as a potential epigenetic modifier.

18 Mar 2025·British Journal of Dermatology

Multitranscriptome analysis reveals stromal cells in the papillary dermis to promote angiogenesis in psoriasis vulgaris

Article

Author: Xu, Xiaoli ; Cai, Zhiming ; Zhou, Fusheng ; Cheng, Hui ; Gao, Min ; Ding, Xiaoyan ; Chen, Gang ; Chen, Mengyun ; Yu, Yafen ; Hu, Weining ; Wu, Chao ; Li, Hui ; Zhu, Caihong ; Liu, Ping ; Wang, Hongyan ; Huang, He ; Zheng, Xiaodong ; Liu, Hui ; Wang, Wenjun ; Rong, Zherou ; Zhou, Shan ; Zhuang, Wen ; Yu, Mengjun ; Mei, Junpu ; Guo, Ze ; Wang, Zaixing ; Zhu, Tingting ; Fang, Xiaodong ; Zhang, Yangrui ; Gao, Jinping ; Tang, Xianfa ; Liao, Qijun ; Li, Yang ; Liu, Shengxiu ; Yue, Zhen ; Tang, Lili ; Zhang, Yin ; Chen, Rouxi ; Fan, Xing ; Wang, Peiguang ; Liu, Xiawei ; Tang, Huayang ; Zhang, Bo

AbstractBackgroundThe pathogenesis of psoriasis is incompletely understood. Growing evidence suggests the involvement of stromal cells in the inflammatory process.ObjectivesTo investigate the roles of stromal cells, including fibroblasts, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), in the psoriatic inflammatory microenvironment, and the possible underlying mechanisms involved.MethodsWe used a combination of single-cell, spatial transcriptome and bulk RNA sequencing of lesional and nonlesional skin samples from patients with psoriasis vulgaris (PV) and healthy skin samples from unaffected individuals.ResultsBy analysing transcriptomes from 364 098 single cells, we uncovered WNT5A+ (Wnt-5a) fibroblasts, ITIH5+ (inter-α-trypsin inhibitor heavy chain 5) VECs and VCAN+ (versican) VSMCs, with significantly increased proportions of these cells in the papillary dermis of lesional psoriatic skin. We defined eight unique subclusters of fibroblasts in the skin and observed a shift of WIF1+ (Wnt inhibitory factor 1) fibroblasts toward WNT5A+ fibroblasts, with abnormal activation of the noncanonical Wnt signalling pathway and increased angiogenic and proinflammatory capabilities. VSMCs were able to undergo phenotypic transformation from a contractile to a synthetic phenotype during the development of psoriatic inflammation. ITIH5+ VECs and VCAN+ VSMCs were found to have an essential role in regulating angiogenesis and vascular remodelling in the pathological changes seen in PV. Ligand receptor analyses found that WNT5A+ fibroblasts are extensively implicated in interactions with various skin cell types, especially TIH5+ VECs and VCAN+ VSMCs in the papillary dermis.ConclusionsInteractions of stromal cells in the papillary dermis were identified as possible pathogenic elements in PV. Improving the inflammatory microenvironment by targeting stromal cells might be a potential treatment strategy in PV.

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WIF1

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