Ask about this productRelated genes to: FGF4 protein
- Gene:
- FGF4 NIH gene
- Name:
- fibroblast growth factor 4
- Previous symbol:
- HSTF1
- Synonyms:
- K-FGF, HBGF-4, HST, HST-1, KFGF
- Chromosome:
- 11q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1988-04-20
- Date modifiied:
- 2014-11-19
Related products to: FGF4 protein
Related articles to: FGF4 protein
- Heatstroke (HS) represents a life-threatening hyperthermic emergency that often leads to multiple organ dysfunction syndrome (MODS), yet no specific pharmacotherapy exists to interrupt this progression. Recent evidence has identified ZBP1-mediated programmed necrosis as a key contributor to organ failure in severe HS, highlighting the critical need for agents that can inhibit this pathway. This study aimed to investigate whether fibroblast growth factor 4 (FGF4) could mitigate HS-induced MODS and to clarify the underlying molecular mechanisms. Using complementary in vitro and in vivo models, along with gene knockdown, proximity ligation, and immunoprecipitation assays, this study indicates that FGF4 significantly reduces multi-organ injury caused by heat stress. Mechanistically, FGF4 interacts with its receptor to activate the AMPK signaling pathway, leading to the phosphorylation of HSF1 at Ser121, which impairs HSF1 nuclear translocation and transcriptional activity, ultimately decreasing ZBP1 expression and inhibiting ZBP1-dependent programmed necrosis. Given the short half-life of native FGF4, a major obstacle for clinical application, a sustained-release nano-liposomal formulation (FGF4-Nano) was engineered using DEPE-PEG2000. This nano-formulation maintains full bioactivity and demonstrates enhanced therapeutic efficacy in HS models, as evidenced by reduced tissue necrosis, improved liver and renal function, and diminished inflammatory damage. Collectively, this work positions FGF4 as a novel suppressor of ZBP1-mediated necrosis, elucidates the mechanistic basis for its actions, and introduces a nano-delivery strategy that significantly amplifies its anti-HS potential, setting the stage for a targeted therapeutic intervention in severe heatstroke. - Source: PubMed
Publication date: 2026/09/28
Wang WenYiCui LeiWang CongLinLuo DiZhang YiRanWang XiaoFeiZhao Hejun - Oral cavity squamous cell carcinoma (OCSCC) is a common epithelial malignancy for which site-specific biomarkers with proven prognostic utility remain limited. In this study, we present one of the largest single-center, site-specific molecular analyses of OCSCC to date. Using two separate versions of multigene next-generation sequencing (NGS), we sought to identify a focused set of clinically actionable and widely accessible biomarkers that could support diagnosis, prognostication, and therapeutic decision-making. Our findings highlight the potential of a limited molecular panel to capture key prognostic information, supporting a more accessible and scalable approach to precision oncology in OCSCC. - Source: PubMed
Publication date: 2026/09/18
Afkhami MichelleHaghighi NMa HReyes AFei FDyer TTelatar MArias-Romero JHaghighi YMehrazma AMassarelli EBakkar RTizro PBell DVillaflor V M - Heparan sulfate proteoglycans (HSPGs) facilitate interactions between growth factors and their receptors, regulating signaling pathways involved in angiogenesis and cell proliferation. However, the structural heterogeneity and synthetic inaccessibility of native heparan sulfate (HS) have limited systematic exploration of structure-activity relationships (SAR) and the discovery of HS-based inhibitors. Here, we developed 46 aminoglycoside-derived non-native HS mimetics spanning diverse structural and functional group patterns. SAR analysis identified N-acetylation and 6-O-sulfation as key determinants of HS-FGF2 and HS-VEGF165 interaction modulation. Compound 8, synthesized in two steps, competitively disrupted heparin binding to FGF2 (IC50 = 0.23 μM), FGFR1 (IC50 = 0.17 μM), and VEGF165 (IC50 = 0.66 μM), with >140-fold FGF2/FGF4 selectivity and substantially greater potency than native HS pentasaccharide fondaparinux. In NIH3T3 fibroblasts, compound 8 selectively reduced FGF2-induced proliferation in a dose-dependent manner without measurable cytotoxicity, highlighting aminoglycoside-derived HS mimetics as synthetically accessible platforms for modulating growth factor signaling. - Source: PubMed
Wakpal JosephSingh KartikeyHotor MichaelPhilip LiviaYost-Slinker DylanWang JunzheAbdulsalam HawauNguyen Hien M - Environmental toxicants (ENVOTOX) have emerged as critical risk factors for congenital malformations (CMFs) in the modern industrial era. Although epidemiological evidence underscores their adverse impact on pregnancy outcomes, the underlying molecular mechanisms remain insufficiently defined. This review consolidates current insights into exposome toxicity profiling, developmental pathway disruptions, and molecular mapping to identify potential biomarkers and mechanistic links between ENVOTOX and CMFs. Protein-protein interaction (PPI) network analysis identified 35 CMF-associated proteins, with ten fibroblast growth factors (FGFs: FGF4, FGF5, FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22) prioritized as hub nodes. Molecular docking analysis showed high binding affinity of FGF9 and FGF4 toward dioxin-associated toxicants, with dibenzo-p-dioxin (DBPDO) exhibiting the strongest interaction (binding energy: -7.2 kcal/mol), followed by polychlorinated dibenzofurans (PCDBFs) (-6.7 kcal/mol) with FGF9. Notably, FGF9 exhibited mutagenic binding potential at ASN146, mediated through π-donor hydrogen bonding with DBPDO. Comparative toxicity data further highlighted the acute risks, as DBPDO demonstrated a lower LD (2.26 mol/kg) relative to PCDBFs (4.134 mol/kg). Collectively, this review emphasizes the central role of FGFs in mediating ENVOTOX-induced teratogenicity and offers molecular-level perspectives to guide biomarker discovery and intervention strategies for mitigating CMF risk. - Source: PubMed
Shukla Adarsh KumarMahajan RashmiTyagi Anuj KumarSwaroop Kamendra - Bone marrow aspirate concentrate (BMAC) is a promising orthobiologic therapy, yet the impact of patient demographics on its proteomic profile remains poorly understood. This study investigates how smoking status, age, sex, and BMI modulate BMAC's protein composition, focusing on 109 analytes across inflammation, immune response, and tissue regeneration pathways. BMAC samples from 120 patients (iliac crest: n = 77; humeral head: n = 43) were stratified by smoking status (current, former, never-smokers) and analyzed via antibody microarrays. Nonparametric statistical analyses (Kruskal-Wallis, Dunn's post hoc) with false discovery rate (FDR) corrections revealed significant proteomic alterations in iliac crest-derived BMAC from smokers, including upregulated pro-inflammatory cytokines (IL-17, TNF-α; p < 0.05, FDR-adjusted) and downregulated anabolic factors (TGF-β1, BMP-9). Former smokers exhibited intermediate profiles, suggesting partial recovery postcessation. Sex-based differences (e.g., BMP-5, FGF-4) were noted but did not survive FDR correction. Humeral head samples showed minimal smoking-related changes, highlighting site-specific effects. These findings underscore smoking's catabolic influence on BMAC's therapeutic potential and advocate for pretreatment cessation protocols. - Source: PubMed
Herna ColinCipriani MadisonSachdev RanjanJedlicka Sabrina