Regenerative repair following tissue injury depends on tightly coordinated signaling networks that determine whether healing culminates in functional restoration or fibrotic scarring. Among these regulators, fibroblast growth factor-2 (FGF2) has emerged as a key modulator of repair outcomes. Mechanistically, FGF2 promotes inflammation resolution, proliferation, vascularization, and re-epithelialization. A central feature of its activity is dynamic cross-talk with transforming growth factor-β (TGF-β), a dominant driver of extracellular matrix deposition and fibrosis. Accumulating evidence indicates that FGF2 inhibits TGF-β-mediated profibrotic signaling, thereby shifting tissue remodeling toward regeneration rather than pathological outcomes. This interaction is supported by both preclinical and clinical evidence showing that FGF2 accelerates wound closure and improves scar architecture. However, despite the compelling biological rationale, the widespread clinical translation of FGF2 has been limited by rapid protein degradation and concerns about proliferative signaling in oncogenic contexts. These limitations have constrained its incorporation into standard therapeutic strategies for chronic wounds and fibrotic disorders. This review provides a synthesis of current mechanistic insights into FGF2 signaling and elucidates its regulatory interplay with TGF-β that favors regenerative repair over fibrosis. We evaluated clinical trial evidence and examined next-generation strategies to overcome translational barriers, including molecular engineering, chimeric growth factor design, and advanced stabilization approaches. By clarifying the regulatory role of FGF2 in the repair trajectory, we highlight its potential to recalibrate fibrotic responses and improve regenerative outcomes.

Fibroblast growth factor receptor 1 (FGFR1) is a cell surface receptor tyrosine kinase implicated in cellular signaling and homeostasis. Several reports indicate that N-glycosylation of FGFR1 is critical for the FGFR1 trafficking to the cell surface, as glycosylation-deficient mutant of FGFR1 (FGFR1.GF) is trapped inside the cell, in the endoplasmic reticulum (ER), and in the nuclear envelope. Our recent mass spectrometry analyses revealed dehydrogenase/reductase 2 (DHRS2) as a putative binding partner of the intracellular FGFR1.GF. Here, we identified a peroxisomal targeting signal 1 (PTS1) at the C-terminus of DHRS2 and demonstrated that DHRS2 is dually targeted to peroxisomes and mitochondria. Furthermore, we determined that knockdown of DHRS2 results in increased number of peroxisomes, implicating the role of DHRS2 in peroxisome biogenesis. Using proximity ligation assay (PLA), we confirmed the interaction between FGFR1.GF and DHRS2 and demonstrated that FGFR1.GF/DHRS2 complexes are predominantly detected in peroxisomes. In agreement, we detected a small fraction of FGFR1.GF in peroxisomes. Taken together our data indicate that accumulation of FGFR1.GF in the ER may result in FGFR1.GF targeting to peroxisomes. Furthermore, we reveal interconnection between FGFR1 and DHRS2 and their role in peroxisome biogenesis.

FGFR2-responsive self-assembled hydrogel releases its inhibitor to suppress the progression of endometriosis.

Circadian disruption is linked to colorectal cancer (CRC) progression. We investigated the role of the tumor suppressor N-myc downstream-regulated gene 2 (NDRG2) in this context. Intestinal-specific Ndrg2 knockout exacerbated colorectal tumorigenesis in mice under circadian disruption. We identified NDRG2 as a novel stabilizer of the core clock protein Circadian Locomotor Output Cycles Kaput (CLOCK). Mechanistically, NDRG2 bidirectionally regulates CLOCK ubiquitination, inhibiting its degradation by the E3 ligase STIP1 Homology and U-Box Containing Protein 1 (STUB1) while promoting stabilization by the deubiquitinase Ubiquitin Specific Peptidase 8 (USP8). This NDRG2-CLOCK axis was crucial for oxaliplatin sensitivity. Integrated RNA sequencing and functional studies revealed that CLOCK transcriptionally represses Fibroblast Growth Factor 2 (FGF2), a chemoresistance driver. Thus, NDRG2 enhances CLOCK activity to suppress FGF2 and promote oxaliplatin efficacy. Clinically, oxaliplatin-sensitive CRC tissues showed higher NDRG2/CLOCK co-expression and lower FGF2 levels. Our work defines a pathway wherein NDRG2 inhibits tumorigenesis and chemoresistance by stabilizing CLOCK to transcriptionally represses FGF2, linking circadian regulation to therapy response, and nominating the NDRG2-STUB1/USP8-CLOCK-FGF2 axis as a therapeutic target.

Synthesis of sulfated α-(1→4)-ʟ-idose oligosaccharides as heparan sulfate mimetics and their interactions with fibroblast growth factors.

Impaired Neurosphere Formation as a Functional Readout of Aberrant EGFR Signaling Kinetics in Olfactory Neural Progenitors From Patients With Schizophrenia.

The emerging role of FGF21 in alcohol consumption and dependence: mechanisms and therapeutic prospects.

Profiling the T cell response to polypropylene mesh in a non-human primate sacrocolpopexy model.

Efficacy and safety of Burosumab in tumor-induced osteomalacia: A systematic review and meta-analysis.

This is the first global report of a successful case of lenvatinib treatment for a rare sebaceous carcinoma originating in the external auditory canal. The patient experienced local recurrence and pulmonary metastasis despite undergoing surgery and radiotherapy. Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.

The processes regulating cellular dormancy in tumor cells remain inadequately characterized. Further, there are very few models available that can recapitulate a dormancy-like phenotype invitro. In this study, we investigated the role of microenvironmental cues in inducing a dormancy-like phenotype in estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. We characterized an invitro model in distinct conditions defined hierarchically by the following: (a) normoxia or true hypoxia, (b) dishes coated with fibronectin or laminin or none, and (c) presence or absence of 10 ng/mL basic fibroblast growth factor (FGF-2) in the culture medium, added on day 0 of culture. Cells were cultured at clonogenic densities for 9 days (day -1, day 0, up to day +7). Cells were characterized for dormancy- like behavior using increased p-p38 and decreased p-ERK expression (dormant, p-p38High and p-ERKLow expression), reduced Ki67 expression, elevated p21 and p27 levels by immunofluorescence, absence of senescence using β-galactosidase staining and resistance to doxorubicin. Fibronectin or laminin were sufficient for the induction of a dormancy-like phenotype in MCF-7 cells under hypoxic conditions, whereas the addition of FGF-2 to fibronectin (but not laminin) could induce a dormancy-like phenotype under normoxic conditions. FGF-2 was required with laminin to induce dormancy in MDA-MB-231 cells under hypoxic conditions (FGF-2 plus fibronectin were unable to induce dormancy), whereas laminin or fibronectin alone were sufficient under normoxic conditions. Overall, we established culture conditions that recapitulate an invitro breast cancer dormancy-like phenotype and reveal subtype-specific differences in dormancy regulation.

Injectable photo-crosslinked hyaluronic acid/carboxymethyl cellulose hydrogel for the sustained delivery of rhFGF2 and accelerated wound healing.

Age-specific centiles for fibroblast growth factor 23 and its associations with mineral and bone metabolism in healthy children.

FGF8 accelerates osteoarthritic chondrocyte hypertrophy by JunB-mediated cytokine perturbation.

Parathyroid hormone (PTH) regulates mineral metabolism and bone strength. Beyond the well-characterized roles of calcium, phosphate, vitamin D, and fibroblast growth factor 23 (FGF23), emerging evidence identifies leptin as a previously under-recognized parathyroid regulator, Secondary hyperparathyroidism (SHP) is a major complication of chronic kidney disease (CKD) characterized by dysregulated PTH secretion and parathyroid hyperplasia. The intracellular signaling mechanisms driving SHP remain elusive. This review examines the role of leptin in PTH regulation and parathyroid physiology and highlights experimental and clinical evidence identifying mechanistic target of rapamycin complex 1 (mTORC1) as a critical regulator of parathyroid structure and function in CKD-SHP. Leptin has been shown to directly stimulate PTH secretion, at least in part by downregulating calcium-sensing receptor (CaSR) signaling, establishing a novel leptin-PTH axis. In experimental CKD, uremia triggers robust parathyroid mTORC1 activation, promoting cellular hyperplasia and PTH overproduction both of which are prevented and reversed by rapamycin. Genetic mouse models show that parathyroid-specific mTOR deletion impairs gland integrity and adaptive PTH responses, whereas constitutive mTORC1 activation via Tsc1 deletion induces autonomous gland enlargement and impaired secretory capacity. Clinically, kidney transplant recipients treated with mTOR inhibitors exhibit lower PTH levels and reduced SHP incidence compared to those receiving other immunosuppressants. mTORC1 is a central integrator of parathyroid growth, structural integrity and hormone secretion. Targeting mTORC1 signaling offers a promising therapeutic strategy for the prevention and management of CKD-associated SHP.

Effects of spermine on osteoblasts during iron deficiency in vitro and in vivo during chronic kidney disease.

To establish a UK consensus vision of a standardised genomic testing pathway in unresectable/metastatic urothelial cancer (mUC) with clear roles and responsibilities for multidisciplinary team (MDT) members and molecular pathology laboratory teams, and to agree how the pathway must evolve to accommodate emerging innovations. A modified Delphi method was used. Six healthcare professionals (HCPs) with expertise in UC formed the Steering Committee (SC), which met in May 2025. Seven key consensus topics were developed covering the steps of the pre-testing and genomic testing pathways, the current and future state of precision medicine, and approaches to overcome barriers and ensure readiness for the future. Within these topics, statements were developed and distributed to clinical scientists and HCPs via an on-line 4-point Likert scale survey. Respondents could opt out of responding to statements outside their area of expertise. Consensus was pre-defined as ≥75% agreement. Overall, 50 responses were received; consensus was reached on 41/42 statements. The statement that did not achieve consensus was part of a paired set. A proposed pathway for pre-testing and genomic testing in unresectable or mUC was developed based on survey results and discussions at SC meetings. Key priorities for the pathway include: timely fibroblast growth factor receptor 3 testing, ideally at the commencement of first-line systemic therapies; selection of specimens based on volume of tissue and recency; immediate access to the genomic testing report for all MDT members; and secure data environments with federated access to genomic results. Since the stopping criteria were met, no further survey rounds were required. Adopting the genomic testing pathway derived from this Delphi consensus will provide greater clarity around MDT and molecular laboratory responsibilities, reduce regional inequities in access, and optimise patient outcomes through timely delivery of genomic testing and subsequent treatment.

Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and fetal outcomes. Although the prevalence of GDM is high, the molecular mechanisms involved in GDM-related placental dysfunction remain poorly understood. This study aimed to investigate the roles of Forkhead box O1 (FoxO1) and fibroblast growth factor 12 (FGF12; a non-FGF receptor) in regulating trophoblast survival under GDM conditions. Placental tissue from women with GDM and matched non-GDM controls were collected to assess FGF12 expression. HTR8/SVneo trophoblast cells under high-glucose conditions were used to assess cellular functional assays, including proliferation, migration, and apoptosis, following FGF12 knockdown or overexpression. The level of FGF12 was significantly attenuated in placental tissues from GDM cases. Silencing FGF12 decreased trophoblast growth and migration, and increased apoptosis induced by high glucose, while FGF12 overexpression reversed these effects. Mechanistically, FoxO1 directly bound to the FGF12 promoter, downregulated its expression. In placental samples from GDM pregnancies, FoxO1 expression was negatively correlated with FGF12 levels. Furthermore, FoxO1 inhibited trophoblast proliferation and migration, while FGF12 overexpression partially rescued the inhibitory effects of FoxO1. These findings suggest that the FoxO1/FGF12 pathway may contribute to impaired trophoblast function in GDM. This study provides preliminary evidence for a regulatable molecular pathway involved in GDM-associated placental dysfunction; however, further validation in larger cohorts and physiologically relevant models is required before clinical applications can be applied.

Expression patterns of CXCR4, ITGB1, and FGFR3 in feline spermatogonial stem cells.

Fibroblast growth factor 21 is differentially expressed in flank skin and regulates the proliferation of hair follicles in yak.