A5101416787- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Neuroscience of respiration and sleep
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Proteoglycans and glycosaminoglycans research
- Drug Transport and Resistance Mechanisms
Wenzhou Medical University
2017-2025
Zhejiang Lab
2023
New York University
2017
Highlights•FGF1-FGFR dimer stability dictates mitogenic versus metabolic functions of FGF1•Proliferative response requires robust and long-lived FGF1-FGFR dimerization•Weak transient dimerization is sufficient for a responseSummaryThe recent discovery roles fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the this classically known mitogen. To dissect molecular basis functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1ΔHBS) that...
Abstract Several members of the FGF family have been identified as potential regulators glucose homeostasis. We previously reported that a low threshold FGF-induced receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke lowering activity. therefore reasoned ligand identity may not matter, besides paracrine FGF1 endocrine FGF21, other cognate FGFs FGFR1c might possess such Indeed, via side-by-side testing multiple in diabetic mice we FGF4 potent anti-hyperglycemic FGF....
Understanding the molecular mechanisms that regulate intestinal epithelial cell (IEC) renewal provides potential targets for inflammatory bowel disease (IBD). Growing evidence has highlighted importance of signals in regulating stem (ISC) differentiation. However, it remains unclear which IEC-derived cytokines can precisely ISC commitment toward specific mature cells. Here we systematically analyze all fibroblast growth factors (FGFs) expression and find colonic FGF1 levels are inversely...
The development of a clinically useful fibroblast growth factor 21 (FGF21) hormone has been impeded by its inherent instability and weak FGF receptor (FGFR) binding affinity. There is an urgent need for innovative approaches to overcome these limitations.We devised structure-based chimerisation strategy in which we substituted the thermally labile low affinity core FGF21 with HS deficient endocrinised derived from stable high paracrine FGF1 (FGF1ΔHBS). thermal stability, ability, heparan...
Significance In this study, we posited that the metabolic and mitogenic activities of enterokine FGF19 are reflections different thresholds FGF19-induced FGF receptor (FGFR) dimerization. To test our hypothesis, engineered three variants have progressively reduced FGFR dimerization capacity. We show these cell proliferative/tumorigenic activity but maintain WT -like activities. These observations substantiate model in which signaling specificity is regulated by FGF-induced dimer stability...
The major safety concern of the clinical application wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis.We found that, similar FGF19WT, chronic administration protects mice from cholestatic...
Endocrine fibroblast growth factor (FGF) 19 has been shown to be capable of maintaining bile acid (BA) homeostasis and thus hold promise a potential therapeutic agent for cholestasis liver disease. However, whether paracrine FGFs possess this BA regulatory activity remains determined. In our study, we identified that 1 (FGF1) was selectively down-regulated in the alpha naphthylisothiocyanate (ANIT) -induced intrahepatic mice, suggesting pathological relevance FGF with abnormal metabolism....
Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) acute failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects pathophysiology. The aim this study to investigate FGFs pathogenesis isoniazid (INH) (RIF)-induced injury. Through systematic screening, finds hepatic FGF1 expression...