FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation

Wang, Dezhong; Jin, Mengyun; Zhao, Xinyu; Zhao, Tianyang; Lin, Wei; He, Zhengle; Fan, Miaojuan; Jin, Wei; Zhou, Jie; Jin, Lingwei; Zheng, Chao; Jin, Hui; Zhao, Yushuo; Li, Xiaokun; Lei, Ying; Wang, Yang; Zhu, Guo‐Qing; Huang, Zhifeng

doi:10.1038/s41419-019-1696-9

Cited by 64 publications

(52 citation statements)

References 63 publications

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“…486,487 Recently, Huang et al 488 engineered the FGF1 mutants (termed FGF1 ΔHBS ) with reduced ability to activate FGFR, and found that FGF1 ΔHBS inhibited inflammation and oxidative stress in CKD via activating PI3K/AKT and GSK-3β/Nrf2 signaling pathways, which inhibited the ASK1/JNK. 489 The results suggest that FGF1 bears the responsibility of anti-inflammation, especially in certain chronic inflammatory diseases. Besides, FGF1 has the ability of anti-inflammation in diabetic nephropathy via inhibition of JNK (c-Jun N-terminal kinase) and NF-κB pathways.…”

Section: Fgf Signaling In Inflammatory Responsementioning

confidence: 96%

FGF/FGFR signaling in health and disease

Xie

Yang

et al. 2020

Sig Transduct Target Ther

454

391

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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, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.

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Section: Fgf Signaling In Inflammatory Responsementioning

confidence: 96%

FGF/FGFR signaling in health and disease

Xie

Yang

et al. 2020

Sig Transduct Target Ther

454

391

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“…On the other hand, treatment with the peptide hormone Elabela activated PI3K/Akt/mTOR and reduced renal inflammation in diabetic mice by decreasing CCL2, ICAM-1, and TNF-α production [241]. In the same line, an engineered partial agonist of fibroblast growth factor-1 (FGF1 ∆HBS ) showed antioxidative effects and anti-inflammatory activities in db/db mice and also reduced oxidative stress and proinflammatory gene expression in podocytes challenged with high glucose by activating PI3K/Akt signaling [242]. Resveratrol has also shown to prevent experimental DN by regulating PI3K/Akt components in kidney tissue [243].…”

Section: Pi3k/akt/mtormentioning

confidence: 99%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

174

127

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Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

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“…Both inflammation and oxidative stress are reported to be closely associated with HG-induced podocyte injury in the development of DN. 18,19 The amplified and continued production of inflammatory cytokines including TNF-α, IL-1β and IL-6 can be induced by exposure of podocytes to HG. 20 Additionally, NLRP3 inflammasome is known to act as a sensor and is shown to be involved in inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

Xue¹,

Mao²,

Chen³

et al. 2020

DMSO

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Background: Diabetic nephropathy (DN) is the leading cause of impaired renal function. The purpose of this study was to investigate the effects of Mogroside IIIE (MG IIIE), a cucurbitane-type compound isolated from Siraitia grosvenorii, in high glucose (HG)induced podocytes and the possible mechanisms. Methods: MPC-5 cells were cultured under normal glucose or HG conditions. After treatment with MG IIIE, cell viability was examined using a cell counting kit-8 assay. The contents of inflammatory factors and oxidative stress-related markers were determined using the corresponding kits. Additionally, apoptosis of MPC-5 cells was determined using flow cytometry assay and the levels of apoptosis-associated proteins were evaluated by Western blot analysis. Moreover, the expression of proteins in AMPK/SIRT1 signaling was tested and the compound C, an AMPK inhibitor, was used to study whether the effects of MG IIIE on HG-induced MPC-5 cells were mediated by activation of the AMPK/SIRT1 signaling pathway. Results: MG IIIE elevated the cell viability of HG-induced MPC-5 cells, reduced the concentrations of inflammatory cytokines and decreased the levels of oxidative stressrelated markers. What's more, the apoptosis of podocytes induced by HG was inhibited after MG IIIE intervention, accompanied by the upregulated expression of Bcl-2 and downregulated expression of Bax, cleaved caspase-3 and cleaved caspase-9. It was also found that MG IIIE could activate the AMPK/SIRT1 signaling, but compound C inhibited this pathway and reversed the inhibitory effects of MG IIIE on inflammation, oxidative stress and apoptosis in HG-stimulated podocytes. Conclusion: MG IIIE can alleviate HG-induced inflammation and oxidative stress of podocytes by the activation of AMPK-SIRT1 signaling.

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FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation

Cited by 64 publications

References 63 publications

FGF/FGFR signaling in health and disease

FGF/FGFR signaling in health and disease

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

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