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Fibroblast growth factor 21 (FGF-21) is a major paracrine and endocrine regulator of metabolic homeostasis. Here we demonstrate that FGF-21 is also a potent mediator of innate immunity. Double-staining flow cytometry identified neutrophils and monocytes as the main sources of FGF-21 among circulating leukocytes. Functional assays showed that FGF-21 stimulates phagocytosis and production of reactive oxygen species in neutrophil-like HL-60 cells and monocytic THP-1 cells. The mechanism of action of FGF-21 was observed to involve FGF receptor activation, signal transduction through the PI3K/Akt pathway, and stimulation of NADPH oxidase activity. This study indicates that FGF-21 could be an attractive target for the management of inflammatory disorders.
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http://dx.doi.org/10.1007/s12020-014-0502-9 | DOI Listing |
Calcif Tissue Int
September 2025
FirmoLab, Fondazione F.I.R.M.O. Onlus and Stabilimento Chimico Farmaceutico Militare (SCFM), 50141, Florence, Italy.
X-linked hypophosphatemia (XLH) is a rare and progressive disease, due to inactivating mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. These pathogenic variants result in elevated circulating levels of fibroblast growth factor 23 (FGF23), responsible for the main clinical manifestations of XLH, such as hypophosphatemia, skeletal deformities, and mineralization defects. However, XLH also involves muscular disorders (muscle weakness, pain, reduced muscle density, peak strength, and power).
View Article and Find Full Text PDFOncogene
September 2025
Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Forkhead-box-protein P3 (FOXP3) is a key transcription factor in T regulatory cells (Tregs). However, its expression and significance in non-immune stromal cells in the tumor microenvironment remain unclear. Here, we demonstrated FOXP3 expression in stromal fibroblasts of mouse and human gastrointestinal tumors.
View Article and Find Full Text PDFOpen Biol
September 2025
National Brain Research Centre, Manesar, Haryana, India.
E3 ubiquitin ligases regulate the cellular proteome proteasome-dependent protein degradation; however, there exist limited studies outlining their non-canonical functions. RNA-binding ubiquitin ligases (RBULs) represent a subset of E3 ligases that harbour RNA-binding domains, making them uniquely positioned to function as both RNA-binding proteins and E3 ligases. Our initial microarray screen for E3 ligases from mouse cortical neural progenitor cells identified MEX3B, a known RNA-binding ubiquitin ligase, to be differentially expressed.
View Article and Find Full Text PDFInt J Pharm
September 2025
CINBIO, Immunology Group, Universidade de Vigo 36310 Vigo, Spain; Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive malignancy with poor therapeutic outcomes due to its desmoplastic tumor microenvironment (TME), hindering drug and activated immune cell penetration. Cancer-associated fibroblasts (CAFs) are central in supporting tumor growth and forming a protective stroma. We propose a novel dual-therapy targeting the Hippo pathway and histone deacetylation, both involved in tumor progression, resistance, and stromal interactions, to overcome PDAC therapeutic resistance.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address:
Skin scar formation is a critical pathological process in wound healing, but its underlying regulatory mechanisms remain incompletely elucidated. By integrating analyses of Bulk-RNA seq and single-cell RNA sequencing (scRNA-seq) data, we identified that ferroptosis-related biological processes potentially play a key role in skin scar formation. Further mechanistic studies demonstrated that in human dermal fibroblast cells, the ferroptosis regulator TIMP metallopeptidase inhibitor 1 (TIMP1) significantly promotes fibroblast differentiation toward a mature phenotype through interactions with cystatin C (CST3), characterized by upregulated expression of myofibroblast differentiation markers such as α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF), along with enhanced cell proliferation and migration abilities.
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