Can targeting the FGF23-αKlotho signaling system delay phosphate-driven organ damage? DOI Creative Commons
Mohammed S. Razzaque, Moosa Mohammadi

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: March 28, 2025

Inexorable high serum phosphate levels in chronic kidney disease (CKD) patients deteriorate the functionality of musculoskeletal, renal, and cardiovascular systems, thereby contributing to increased morbidity mortality. Higher balance has also been correlated with mortality rates individuals normal renal function, independent other comorbidities. Clinical epidemiological studies CKD healthy subjects, alongside evidence accelerated aging murine models induced by excessive loading, indicate that toxicity is a driver premature age-related organ damage. This article briefly discusses causes consequences context damage while elaborating on therapeutic potential fibroblast growth factor 23 (FGF23) hormone signaling system alleviating function CKD. Human age-associated disorders may be delayed through dietary programs or pharmacological interventions capable modulating activity FGF23 reduce systemic burden.

Language: Английский

Distinct Fgf21 Expression Patterns in Various Tissues in Response to Different Dietary Regimens Using a Reporter Mouse Model DOI Open Access
Xinhui Zhang, Zixuan Li,

Shuying Wang

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(7), P. 1179 - 1179

Published: March 28, 2025

Background: Fibroblast growth factor 21 (FGF21), a secreted protein, plays crucial role in regulating metabolism and energy homeostasis. Nevertheless, the expression pattern of Fgf21 across diverse tissues its responsiveness to various dietary regimens remain incompletely understood. Methods: In this study, we developed Fgf21-enhanced green fluorescent protein (EGFP) reporter mouse model explore endogenous different under four conditions: normal chow, low-protein diet, fasting, fasting-refeeding. Results: A diet was found induce both liver skeletal muscle. Notably, predominantly expressed periportal region liver. pancreas, exhibited patchy exocrine portion, but absent endocrine part, regardless regimens. Regarding spleen, fasting triggered Fgf21, which mainly localized red pulp area. Moreover, conditions, showed scattered small intestine. Conclusions: The Fgf21-EGFP serves as valuable tool for dissecting stress conditions. Further investigations using may contribute uncovering hitherto unrecognized functions locally produced FGF21.

Language: Английский

Citations

0
Regulation of epithelial growth factor receptors by the oncoprotein E5 during the HPV16 differentiation-dependent life cycle DOI Creative Commons
Mariano A. Molina,

Sneha Biswas,

Omar Jiménez-Vázquez

et al.

Tumour Virus Research, Journal Year: 2025, Volume and Issue: 19, P. 200315 - 200315

Published: March 7, 2025

Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. expresses oncoproteins E5, E6, and E7 promote immune evasion, cell cycle progression, apoptosis inhibition, replication. least studied oncoprotein is E5 (16E5), can regulate epithelial growth factor receptor (GFR) pathways. GFRs such as transforming factor-beta (TGFBR), epidermal (EGFR), keratinocyte (KGFR) have essential roles in growth, differentiation, proliferation. These receptors obtain their ligands from microenvironment, once activated, behavior therefore represent valuable targets for establish maintain a environment supportive infection. ability 16E5 proliferation differentiation varies through differentiating epithelium, making it necessary adequately describe association between GFRs. Here we summarize regulation GFR by 16E5, discuss stromal factors, outline unresolved questions over during HPV cycle.

Language: Английский

Citations

0
Identifcation of the FGF family as therapeutic targets and prognostic biomarkers in the microenvironment of head and neck squamous cell carcinoma DOI Creative Commons
Li Zhang, Yingchun Gao, Yumei Tian

et al.

SLAS TECHNOLOGY, Journal Year: 2025, Volume and Issue: unknown, P. 100271 - 100271

Published: March 1, 2025

Almost 90% of head and neck malignancies are malignant squamous cell cancers, making it the sixth most common malignancy in developing countries, with an overall five-year survival rate about 40%-50%. Early diagnosis treatment can bring a better prognosis. Fibroblast growth factor (FGF) is important polypeptide vivo. Studies have found that FGF signal has carcinogenic potential participates variety behaviors. Some experiments proved function tumor inhibition some cases, role signalling tissue repair homeostasis suggest for targeted therapy However, its manifestation predictive HNSC not been clearly defined. Genome-wide expression analysis Oncomine evaluated evaluation family HNSC. Expression data set were used to obtain T statistic was applied analysis. The differential mRNA levels versus normal tissues, as well correlation pathological staging prognosis, examined using GEPIA single-gene tool family.FGF altered CO network modules obtained from cBioportal analyzed 520 samples.Pro-protein interaction (PPI) flow performed on differentially ordered clusters STRING, Gene Operating System (GO) domain enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway cluster neighbouring genes DAVID6.8, key transcriptional factors (TF) by TRRUST, between level autoimmune migration TIMER, biological kinase target LinkInterpreter. Only FGF6 down-regulated all family(FC=2),Transcriptional FGF1, FGF2, FGF5, FGF7-14, FGF17-19, FGF21 FGF22 upregulated .In terms relative HNSC, greatest amount FGF11. In different stages meaningless (P>0.05), FGF3-6, FGF8-10, FGF14, FGF16, FGF17, FGF19 -21, FGF23 showed no significant difference stages. Low FGF5 high had low survival(OS) HNSC(P =0.012, P =0.0015). addition, highly abundant PI3K-Akt signaling pathway, MAPK rasper pathway. Our ATF4, STAT, RELA, NFKB1 transcription family, NLK, LOCK1, LYN, ZAP70, MAP2K3, RPS6KA4, AURKB, ATR, ROCK1, MYLK2, CAMK2A, EGFR, MAPK3, MAP3K8, SYK, LCK, HCK, PKN2, RPS6KA1, BUB1, CDK5, ITK, FYN, TBK1, ATM, CDK2, PTK2 targets family. We identified relationship modulation cellular infiltration, such B lymphocytes, CD4+ cells macrophages dendritic cells. may shed new light choice immunotherapeutic biomarkers

Language: Английский

Citations

0
Can targeting the FGF23-αKlotho signaling system delay phosphate-driven organ damage? DOI Creative Commons
Mohammed S. Razzaque, Moosa Mohammadi

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: March 28, 2025

Inexorable high serum phosphate levels in chronic kidney disease (CKD) patients deteriorate the functionality of musculoskeletal, renal, and cardiovascular systems, thereby contributing to increased morbidity mortality. Higher balance has also been correlated with mortality rates individuals normal renal function, independent other comorbidities. Clinical epidemiological studies CKD healthy subjects, alongside evidence accelerated aging murine models induced by excessive loading, indicate that toxicity is a driver premature age-related organ damage. This article briefly discusses causes consequences context damage while elaborating on therapeutic potential fibroblast growth factor 23 (FGF23) hormone signaling system alleviating function CKD. Human age-associated disorders may be delayed through dietary programs or pharmacological interventions capable modulating activity FGF23 reduce systemic burden.

Language: Английский

Citations

0