FGF/FGFR signaling in health and disease

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Сен. 2, 2020

Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, apoptosis various types cells. In this review, we provide comprehensive overview current understanding FGF its organ development, injury repair, pathophysiology spectrum diseases, which is consequence dysregulation, including cancers chronic kidney disease (CKD). context, agonists antagonists for FGF-FGFRs might have therapeutic benefits multiple systems.

Язык: Английский

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Physical Activity and Brain Health

Genes, Год журнала: 2019, Номер 10(9), С. 720 - 720

Опубликована: Сен. 17, 2019

Physical activity (PA) has been central in the life of our species for most its history, and thus shaped physiology during evolution. However, only recently health consequences a sedentary lifestyle, highly energetic diets, are becoming clear. It also acknowledged that lifestyle diet can induce epigenetic modifications which modify chromatin structure gene expression, causing even heritable metabolic outcomes. Many studies have shown PA reverse at least some unwanted effects contribute delaying brain aging degenerative pathologies such as Alzheimer’s Disease, diabetes, multiple sclerosis. Most importantly, improves cognitive processes memory, analgesic antidepressant effects, induces sense wellbeing, giving strength to ancient principle “mens sana corpore sano” (i.e., sound mind body). In this review we will discuss potential mechanisms underlying on health, focusing hormones, neurotrophins, neurotransmitters, release is modulated by PA, well intra- extra-cellular pathways regulate expression genes involved.

Язык: Английский

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Mechanisms of cognitive dysfunction in CKD

Nature Reviews Nephrology, Год журнала: 2020, Номер 16(8), С. 452 - 469

Опубликована: Март 31, 2020

Язык: Английский

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Inflammation and Premature Ageing in Chronic Kidney Disease

Toxins, Год журнала: 2020, Номер 12(4), С. 227 - 227

Опубликована: Апрель 4, 2020

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype contribute to impaired health status, reduced quality life, mortality in chronic kidney disease (CKD). Because there is a huge global burden due CKD, treatment strategies targeting CKD particular interest. Several distinct features may represent potential options attenuate risk progression poor outcome CKD. The nuclear factor erythroid 2-related 2 (NRF2)–kelch-like cell-derived protein with CNC homology [ECH]-associated 1 (KEAP1) signaling pathway, endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, mitochondrial biogenesis currently most promising candidates, different pharmaceutical compounds already under evaluation. If studies humans show beneficial effects, carefully phenotyped patients can benefit from them.

Язык: Английский

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Klotho, Aging, and the Failing Kidney

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Авг. 27, 2020

Klotho has been recognised as a gene involved in the ageing process mammals for over thirty years, where it regulates phosphate homeostasis and activity of members fibroblast growth factor (FGF) family. The α -Klotho protein is receptor Fibroblast Growth Factor-23 (FGF23), regulating vitamin D metabolism. Phosphate toxicity hallmark mammalian correlates with diminution levels increasing age. As such, modulation an attractive target therapeutic intervention diseasome ageing; particular chronic kidney disease (CKD), implicated directly pathophysiology. A range senotherapeutic strategies have developed to or indirectly influence expression, varying degrees success. These include administration exogenous Klotho, synthetic natural agonists indirect approaches, via foodome gut microbiota. All these approaches significant potential mitigate loss physiological function resilience accompanying old age improve outcomes within ageing.

Язык: Английский

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High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Cell, Год журнала: 2020, Номер 181(6), С. 1291 - 1306.e19

Опубликована: Май 13, 2020

Язык: Английский

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FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Дек. 14, 2020

The rising global prevalence of obesity, metabolic syndrome, and type 2 diabetes has driven a sharp increase in non-alcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation the liver. Approximately one-sixth NAFLD population progresses to steatohepatitis (NASH) with inflammation, hepatocyte injury cell death, fibrosis cirrhosis. NASH is one leading causes transplant, an increasingly common cause hepatocellular carcinoma (HCC), underscoring need for intervention. complex pathophysiology NASH, predicted 3–5% adult worldwide, prompted drug development programs aimed at multiple targets across all stages disease. Currently, there are no approved therapeutics. Liver-related morbidity mortality highest more advanced fibrotic which led early focus on anti-fibrotic approaches prevent progression cirrhosis HCC. Due limited clinical efficacy, have been superseded mechanisms that target underlying driver pathogenesis, namely steatosis, drives downstream inflammation fibrosis. Among this wave therapeutic targeting pathogenesis hormone fibroblast growth factor 21 (FGF21) holds considerable promise; it decreases while suppressing preclinical studies. In review, we summarize data from studies FGF21 analogs, context diseases.

Язык: Английский

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Receptor tyrosine kinase activation: From the ligand perspective

Current Opinion in Cell Biology, Год журнала: 2020, Номер 63, С. 174 - 185

Опубликована: Фев. 27, 2020

Язык: Английский

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The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration

Cells, Год журнала: 2021, Номер 10(11), С. 3242 - 3242

Опубликована: Ноя. 19, 2021

Fibroblast growth factors (FGFs) are a large family of secretory molecules that act through tyrosine kinase receptors known as FGF receptors. They play crucial roles in wide variety cellular functions, including cell proliferation, survival, metabolism, morphogenesis, and differentiation, well tissue repair regeneration. The signaling pathways regulated by FGFs include RAS/mitogen-activated protein (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)–protein B (AKT), phospholipase C gamma (PLCγ), signal transducer activator transcription (STAT). To date, 22 have been discovered, involved different functions the body. Several directly or indirectly interfere with during regeneration, addition to their critical maintenance pluripotency dedifferentiation stem cells. In this review, we summarize diverse processes shed light on importance mechanisms

Язык: Английский

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Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Frontiers in Aging, Год журнала: 2022, Номер 3

Опубликована: Июль 12, 2022

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These have shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of opposite effects, extending lifespan. In humans, levels decline with age, chronic kidney diabetes, Alzheimer's disease other conditions. Low correlate an increase the death rate from all causes. acts either obligate coreceptor fibroblast growth factor 23 (FGF23), or soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced kidneys, but also brain, pancreas tissues. On tubular-cell membranes, it associates FGF receptors to bind FGF23. Produced bones, FGF23 regulates excretion phosphate (phosphaturic effect) vitamin D metabolism. Lack results hyperphosphatemia hypervitaminosis D. With human function often deteriorates, lowering levels. This appears promote age-related pathology. Remarkably, inhibits four pathways that been linked aging various ways: Transforming β (TGF-β), insulin-like 1 (IGF-1), Wnt NF-κB. can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis neoplasia. Furthermore, increases cell-protective antioxidant enzymes through Nrf2 FoxO. accord, preclinical therapy ameliorated renal, cardiovascular, diabetes-related neurodegenerative diseases, well cancer. s-Klotho injection was effective, requires further investigation. Several drugs enhance circulating levels, some cross blood-brain barrier potentially act brain. clinical trials, increased noted renin-angiotensin system inhibitors (losartan, valsartan), statin (fluvastatin), mTOR (rapamycin, everolimus), pentoxifylline. work, antidiabetic (metformin, GLP-1-based, GABA, PPAR-γ agonists) enhanced Klotho. traditional medicines and/or nutraceuticals rodents, including astaxanthin, curcumin, ginseng, ligustilide resveratrol. Notably, exercise sport activity review addresses molecular, physiological therapeutic aspects

Язык: Английский

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