Ask about this productRelated genes to: WNT4 antibody
- Gene:
- WNT4 NIH gene
- Name:
- Wnt family member 4
- Previous symbol:
- -
- Synonyms:
- WNT-4
- Chromosome:
- 1p36.12
- Locus Type:
- gene with protein product
- Date approved:
- 2000-07-31
- Date modifiied:
- 2016-10-05
Related products to: WNT4 antibody
Related articles to: WNT4 antibody
- To investigate the effects of irisin on the Wnt/β-catenin signaling pathway in the endometrium of obese rats. - Source: PubMed
Zhou LiZhang Ying-JunZhang Xiao-ZheLiu Xian-YunLi Cheng-Gang - The mouse adrenal gland is encapsulated by a mesenchymal cell layer (capsule) and contains an underlying cortex organized into distinct concentric zones with specialized endocrine functions: the zona glomerulosa (zG), which produces aldosterone, and the zona fasciculata (zF), which produces corticosterone. The adrenal medulla, located at the center of the gland, produces catecholamines. Mechanistic studies of cells from each adrenocortical zone have been limited by the absence of in vitro models that preserve their zone-specific molecular, cellular, and functional characteristics. To overcome this limitation, a fractionation approach was developed using microdissection of adult mouse adrenal glands. This method separates adrenal cells from male mice into a zG-enriched outer fraction (OF), containing capsule and zG cells, and a zF-enriched inner fraction (IF), which contains zF and medullary cells. These fractions were used to generate two-dimensional (2D) primary cultures enriched for either zG or zF cells. Gene expression analysis confirmed that the zG-enriched cultures express high levels of zG markers (Cyp11b2, Dab2, and Shh), along with increased Wnt/β-catenin pathway markers (Wnt4, Lef1). In contrast, zF-enriched cultures exhibited higher expression of zF markers (Cyp11b1 and Akr1b7) and lower levels of Wnt/β-catenin pathway markers, consistent with a zF transcriptional signature. Expression of steroidogenic markers (Nr5a1, Star) validated the adrenocortical origin of both cell fractions. Tyrosine hydroxylase indicates the presence of adrenal medullary cells in zF-enriched cultures. Functionally, zG-enriched cultures produced aldosterone under basal conditions and showed increased production in response to angiotensin II, potassium, and adrenocorticotropic hormone (ACTH). Conversely, zF-enriched cultures produced corticosterone at baseline and exhibited increased output in response to ACTH stimulation. Overall, this protocol represents a robust, reproducible, and biologically relevant in vitro model for studying adrenal cortex biology. This system enables zone-specific investigation of signaling pathways, molecular mechanisms, and physiological responses. - Source: PubMed
Publication date: 2026/05/08
Kremer Jean LucasBorges Kleiton SilvaRibeiro ClaudioBerber MesutHaykir BetulCarlone Diana LLotfi Claudimara Ferini PaciccoBreault David T - Chemotherapy-associated gonadotoxicity compromises Leydig cell steroidogenesis and leads to testosterone deficiency, yet repair is hindered by the testicular barrier-immune niche and by limited manufacturability of biologics. Inspired by the tubular architecture of seminiferous tubules, we develop a coaxial bioprinting-enabled encapsulation culture that generates continuous core-shell hydrogel microfibers for high-density 3D culture of human umbilical cord MSCs (hUMSCs) and continuous conditioned-medium harvesting, producing seminiferous tubule-inspired coaxial bioprinting-derived extracellular vesicles (STi-EVs). We directly benchmark STi-EVs against conventional 2D culture-derived EVs (2D-EVs) in a 4-hydroperoxycyclophosphamide (4-HC)-injured TM3 model and a cyclophosphamide-induced mouse model. Across cellular fitness, re-engagement of steroidogenic programs, and testosterone output, STi-EVs consistently outperform 2D-EVs, while more effectively alleviating testicular histopathology and restoring serum testosterone in vivo. Transcriptomics prioritize Wnt signaling and nominate Wnt4; orthogonal validation and Wnt4 gain- and loss-of-function perturbations, and β-catenin stabilization experiments support that modulation of Wnt4/β-catenin signaling functionally contributes to STi-EV-mediated steroidogenic restoration. Collectively, this work couples a scalable extracellular vesicles (EV) manufacturing paradigm with a mechanism-informed repair strategy for endocrine sequelae after alkylating chemotherapy. - Source: PubMed
Publication date: 2026/05/21
Wu JialinChen JianweiTao YiranGuo QiangHuang JiayuZhang YiZhang TianyouMo ZijunWang DejuanXu TaoQiu Jianguang - Inflammation-driven tumor implantation, such as port-site metastasis (PSM) following laparoscopic gynecologic surgery and peritoneal seeding during post-surgical recurrence, represents an aggressive clinical problem that remains poorly understood and lacks targeted therapies. To address this, we developed a non-surgical Mesothelium-Inflammation/Injury-Metastasis (MIM) model and investigated the role of the IL-1β/IL1R1/MYD88/IRAK1/4 axis and NLRP3 in epithelial ovarian cancer (EOC) seeding at inflamed or injured sites. This model created by a needle injury recapitulates inflammation-driven peritoneal seeding and mimics PSM and inflammation associated dissemination in peritoneum during recurrence. Seeding was dependent on Il1r1 but not Nlrp3, despite its role in regulating IL-1β production, as Il1ra⁻/⁻ and Nlrp3⁻/⁻ mice phenocopied wild-type C57BL/6 mice. Given the limited antitumor efficacy of IL-1β-targeting agents such as Anakinra and Canakinumab, we focused on IRAK4 as a therapeutic target. IRAK4 knockdown significantly prolonged survival, reduced tumor cell adhesion, downregulated E-cadherin and Wnt4, and induced S-phase/mitotic arrest. This led to the development of UR241-2, a small-molecule IRAK4 inhibitor, which was validated through molecular simulations, hotspot analysis, nanoBRET, global kinome profiling, and NF-κβ reporter assays. UR241-2 inhibited NF-κβ nuclear translocation and blocked IL-1β-induced IRAK4 phosphorylation. UR241-2 exhibited favorable drug-like properties, including absence of CYP or hERG inhibition, and acceptable CaCo-2 permeability, plasma protein binding, microsomal stability, and pharmacokinetics. In vivo, UR241-2 reduced SKOV3 xenograft growth, suppressed mesothelial seeding, and increased MHC-II⁺ macrophages and activated neutrophils in syngeneic high-grade epithelial ovarian HGS3 tumors. RNA-seq revealed enrichment of neutrophil activation signatures and suppression of extracellular matrix (ECM) gene programs. Together, these findings establish a role for the IL-1β/IL1R1/IRAK4 axis in inflammation-driven PSM and peritoneal seeding and ECM regulation in EOC, and demonstrate that IRAK4 inhibition activates antitumor immune responses, providing a therapeutic strategy to block metastatic seeding and improve tumor control. - Source: PubMed
Publication date: 2026/05/05
Miller John PKim Kyu KwangSnyder Cameron WaKhazan NegarSingh Niloy ABoyer Megan ELamere ElizabethStrawderman MylaSharma SonaliLakony RonaldWhittum MichelleAnderson MarkKeenan RickPritchett ElizabethBaker CameronAshton JohnKhera Manoj KElliott Michael RAnnunziata Christina MBajaj JeevishaCalvi Laura MBecker Michael WRowswell-Turner RachaelMoore Richard GSingh Rakesh K - Titanium dioxide nanoparticles (nano-TiO₂) and carbamazepine (CBZ) are both emerging contaminants of concern in coastal environments. Current monitoring data indicate that nano-TiO₂ occur in nearshore seawater affected by land-based inputs, and CBZ is persistently detected in estuarine and nearshore waters; therefore, these contaminants may co-occur at a regional scale. In this study, the thick-shelled mussel (Mytilus coruscus) was used as a model organism. Nominal concentrations of nano-TiO₂ (100 μg/L) and CBZ (10 μg/L) were applied in single and combined exposure experiments over 14 days. Particle characterization, gonadal morphology, sex steroid hormone levels, and key gene expression analyses were integrated to evaluate reproductive hormone-disrupting effects. The results showed that nano-TiO₂ readily aggregated in seawater, and distinct nano-TiO₂ aggregates were observed on the surface of CBZ crystals in dried mixed samples. Phenotypically, exposure to either pollutant alone reduced the gonadal area and gonadosomatic index, showing significant sex-specific differences in the CBZ group. In contrast, combined exposure caused more pronounced reproductive tissue damage. Hormonally, exposure disrupted sex steroid homeostasis, decreasing progesterone, estrone, and estradiol (E2), accompanied by increased testosterone (T). These hormonal changes exhibited sex-dependent patterns across treatments, with a decrease in E2 and an increase in T being more pronounced in the combined-exposure group. Molecularly, exposures significantly downregulated SF-1 and Wnt signaling genes (β-catenin, Wnt4), while upregulating Wnt7b. Overall, single exposure to nominal concentrations of nano-TiO₂ or CBZ was sufficient to induce sex-specific reproductive damage in M. coruscus, whereas combined exposure caused more pronounced changes at the morphological, hormonal, and transcriptional levels. - Source: PubMed
Publication date: 2026/05/14
Hu ChunLi ZiyinWu GuanglinLee Jae-SeongMiao JingjingDong YunweiMaszczyk PiotrSharifinia MoslemSingh NishaShang YueyongWang Youji