fg-4592 has been researched along with Fibrosis* in 3 studies
3 other study(ies) available for fg-4592 and Fibrosis
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Effect of Roxadustat on Factors Associated with Renal Fibrosis and Efficacy.
We investigated the effect of roxadustat on factors associated with renal fibrosis and efficacy. After giving roxadustat, it can change the expression of HIF-1 Topics: Anemia; Fibrosis; Glycine; Hemoglobins; Hepcidins; Humans; Isoquinolines; Kidney Diseases; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A | 2022 |
Anti-anemia drug FG4592 retards the AKI-to-CKD transition by improving vascular regeneration and antioxidative capability.
Acute kidney injury (AKI) is a known risk factor for the development of chronic kidney disease (CKD), with no satisfactory strategy to prevent the progression of AKI to CKD. Damage to the renal vascular system and subsequent hypoxia are common contributors to both AKI and CKD. Hypoxia-inducible factor (HIF) is reported to protect the kidney from acute ischemic damage and a novel HIF stabilizer, FG4592 (Roxadustat), has become available in the clinic as an anti-anemia drug. However, the role of FG4592 in the AKI-to-CKD transition remains elusive. In the present study, we investigated the role of FG4592 in the AKI-to-CKD transition induced by unilateral kidney ischemia-reperfusion (UIR). The results showed that FG4592, given to mice 3 days after UIR, markedly alleviated kidney fibrosis and enhanced renal vascular regeneration, possibly via activating the HIF-1α/vascular endothelial growth factor A (VEGFA)/VEGF receptor 1 (VEGFR1) signaling pathway and driving the expression of the endogenous antioxidant superoxide dismutase 2 (SOD2). In accordance with the improved renal vascular regeneration and redox balance, the metabolic disorders of the UIR mice kidneys were also attenuated by treatment with FG4592. However, the inflammatory response in the UIR kidneys was not affected significantly by FG4592. Importantly, in the kidneys of CKD patients, we also observed enhanced HIF-1α expression which was positively correlated with the renal levels of VEGFA and SOD2. Together, these findings demonstrated the therapeutic effect of the anti-anemia drug FG4592 in preventing the AKI-to-CKD transition related to ischemia and the redox imbalance. Topics: Acute Kidney Injury; Animals; Antioxidants; Disease Models, Animal; Fibrosis; Glycine; Isoquinolines; Kidney; Male; Mice, Inbred C57BL; Pharmaceutical Preparations; Regeneration; Renal Insufficiency, Chronic; Reperfusion Injury; Vascular Endothelial Growth Factor A | 2021 |
Effects of orally active hypoxia inducible factor alpha prolyl hydroxylase inhibitor, FG4592 on renal fibrogenic potential in mouse unilateral ureteral obstruction model.
Orally active hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors that stabilize HIF protein and stimulate the production of erythropoietin have been approved to treat renal anemia. Our previous report suggested that HIF-1α dependent fibrogenic mechanisms are operating at the early onset of renal fibrosis and its contribution declines with the progression in mouse unilateral ureteral obstruction (UUO) model. The aim of the study is to evaluate the renal fibrogenic potential of FG4592, a recently approved orally active HIF prolyl hydroxylase inhibitor in mouse UUO model. Male C57BL/6J mice orally given FG-4592 (12.5 mg/kg/day and 50 mg/kg/day) were subjected to UUO. Neither dose of FG-4592 affected renal fibrosis or macrophage infiltration. FG-4592 had no effects on increased mRNA of collagen I, collagen III or transforming growth factor-β1. At 3 days after UUO, higher dose of FG-4592 potentiated the increased mRNA expression of profibrogenic molecules, plasminogen activator inhibitor 1 (Pai-1) and connective tissue growth factor (Ctgf) but such potentiation disappeared at 7 days after UUO. It is suggested that FG-4592 used in the present study had little effects on renal fibrosis even though high dose of FG-4592 used in the present study transiently potentiated gene expression of Pai-1 and Ctgf in the UUO kidney. Topics: Administration, Oral; Animals; Fibrosis; Glycine; Hypoxia-Inducible Factor 1, alpha Subunit; Isoquinolines; Kidney; Male; Mice, Inbred C57BL; Prolyl-Hydroxylase Inhibitors; Ureteral Obstruction | 2020 |