FGF and TGF-β growth factor isoform modulation of human gingival and periodontal ligament fibroblast wound healing phenotypeGuo, Rizkalla, Hamilton
Matrix Biol (2025) 136, 9-21
Abstract: Release of growth factors in the tissue microenvironment is a critical process in the repair and regeneration of periodontal tissues, regulating fibroblast behavior and phenotype. As a result of the complex architecture of the periodontium, distinct fibroblast populations in the periodontal ligament and gingival connective tissue exist in close proximity. Growth factor therapies for periodontal regeneration have gained traction, but quantification of their effects on multiple different fibroblast populations that are required for repair has been poorly investigated. In this study, we examined the effects of TGF-β1, TGF-β3, FGF-2, and FGF-9 on human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDL), as well as the combined effects of TGF-β3 and FGF-2. We show that FGF-2 enhances cell migration while TGF-β1 and TGF-β3 promotes matrix production, and TGF-β1 promotes fibroblast to myofibroblast transition. Interestingly, the combination of TGF-β3 and FGF-2, acting through both p-SMAD3 and p-ERK pathways, mitigates the inhibitory effects of TGF-β3 on migration in hPDL cells, suggesting synergistic and complimentary effects of FGF-2 and TGF-β3. Additionally, fibronectin production in hGF increased when treated with the combined TGF-β3+FGF-2 compared to FGF-2 alone, indicating that the effects of TGF-β3 in promoting extracellular matrix production are still active in the combined treatment condition. Finally, our study highlights that FGF-9 did not influence migration, α-SMA expression, or extracellular matrix production in either cell type, emphasizing the unique roles of specific growth factors in cellular responses. The synergistic effects observed with combined TGF-β3 and FGF-2 treatments present promising avenues for further research and clinical advancements in regenerative medicine.Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
The association between insulin resistance and cytokines in adolescents with excess of adiposityRamírez-Vélez, Correa-Rodríguez, Calderón-González
et alCurr Probl Cardiol (2025) 50 (1), 102925
Abstract: Increased adiposity has been directly associated with insulin resistance (IR), and cytokines released by adipose tissue seem to link adiposity to IR in youth. We used an antibody-based array to investigate the differential levels of serum cytokines according to insulin status in a cohort of overweight/obese and inactive adolescents and evaluated their potential associations with clinical and metabolic characteristics.We performed a cross-sectional data analysis from 122 adolescents (11-17 years of age). We assessed body composition, cardiometabolic risk factors, biochemical variables, and physical fitness. The concentration of 55 cytokines was quantified in blood samples. The homeostasis model assessment insulin resistance (HOMA-IR) and AST/ALT and TG/HDL ratios were calculated. IR adolescents as defined as HOMA-IR >2.5. The number of adolescents with IR in the study was 91 (66 % girls). In the IS group, after controlling for confounders, higher IL-15 levels were significantly associated with higher alanine aminotransferase levels and lower AST/ALT ratio, respectively (Ps<0.05). In the same line, there were significantly higher alanine aminotransferase levels and lower AST/ALT ratio, respectively, with FGF-9 (Ps<0.05). Likewise, higher alanine aminotransferase levels were significantly associated positively with HGF (p=0.045). Additionally, leptin levels are associated with six adiposity indexes (i.e., fat mass/height index, body fat, body mass index, android fat mass and gynoid fat mass) in overweight/obese adolescents with IR (Ps<0.05).These data may provide novel insights into the pathogenic mechanisms underlying IR in youth, offering new targets for prevention.Copyright © 2024 Elsevier Inc. All rights reserved.
Mechanistic differences in eukaryotic initiation factor requirements for eIF4GI-driven cap-independent translation of structured mRNAsSaha, Haizel, Goss
J Biol Chem (2024) 300 (11), 107866
Abstract: Protein translation is globally downregulated under stress conditions. Many proteins that are synthesized under stress conditions use a cap-independent translation initiation pathway. A subset of cellular mRNAs that encode for these proteins contain stable secondary structures within their 5'UTR, and initiate cap-independent translation using elements called cap-independent translation enhancers or internal ribosome entry sites within their 5'UTRs. The interaction among initiation factors such as eukaryotic initiation factor 4E (eIF4E), eIF4A, and eIF4GI, especially in regulating the eIF4F complex during noncanonical translation initiation of different 5'UTR mRNAs, is poorly understood. Here, equilibrium-binding assays, CD studies and in vitro translation assays were used to elucidate the recruitment of these initiation factors to the highly structured 5'UTRs of fibroblast-growth factor 9 (FGF-9) and hypoxia inducible factor 1 subunit alpha (HIF-1α) encoding mRNAs. We showed that eIF4A and eIF4E enhanced eIF4GI's binding affinity to the uncapped 5'UTR of HIF-1α mRNA, inducing conformational changes in the protein/RNA complex. In contrast, these factors have no effect on the binding of eIF4GI to the 5'UTR of FGF-9 mRNA. Recently, Izidoro et al. reported that the interaction of 42nt unstructured RNA to human eIF4F complex is dominated by eIF4E and ATP-bound state of eIF4A. Here, we show that structured 5'UTR mRNA binding mitigates this requirement. Based on these observations, we describe two possible cap-independent translation mechanisms for FGF-9 and HIF-1α encoding mRNAs used by cells to mitigate cellular stress conditions.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Discovery of crucial cytokines associated with deep vein thrombus formation by protein array analysisWang, Chi, Zeng
et alBMC Cardiovasc Disord (2024) 24 (1), 374
Abstract: Expanding the number of biomarkers is imperative for studying the etiology and improving venous thromboembolism prediction. In this study, we aimed to identify promising biomarkers or targeted therapies to improve the detection accuracy of early-stage deep vein thrombosis (DVT) or reduce complications.Quantibody Human Cytokine Antibody Array 440 (QAH-CAA-440) was used to screen novel serum-based biomarkers for DVT/non-lower extremity DVT (NDVT). Differentially expressed proteins in DVT were analyzed using bioinformatics methods and validated using a customized array. Diagnostic accuracy was calculated using receiver operating characteristics, and machine learning was applied to establish a biomarker model for evaluating the identified targets. Twelve targets were selected for validation.Cytokine profiling was conducted using a QAH-CAA-440 (RayBiotech, USA) quantimeter array. Cross-tabulation analysis with Venn diagrams identified common differential factors, leading to the selection of 12 cytokines for validation based on their clinical significance. These 12 biomarkers were consistent with the results of previous array analysis: FGF-6 (AUC = 0.956), Galectin-3 (AUC = 0.942), EDA-A2 (AUC = 0.933), CHI3L1 (AUC = 0.911), IL-1 F9 (AUC = 0.898), Dkk-4 (AUC = 0.88), IG-H3 (AUC = 0.876), IGFBP (AUC = 0.858), Gas-1 (AUC = 0.858), Layilin (AUC = 0.849), ULBP-2 (AUC = 0.813)and FGF-9 (AUC = 0.773). These cytokines are expected to serve as biomarkers, targets, or therapeutic targets to differentiate DVT from NDVT.EDA-A2, FGF-6, Dkk-4, IL-1 F9, Galentin-3, Layilin, Big-h3, CHI3L1, ULBP-2, Gas-1, IGFBP-5, and FGF-9 are promising targets for DVT diagnosis and treatment.© 2024. The Author(s).
膜杰作
Star Staining
