Reduction of cellular stress is essential for Fibroblast growth factor 1 treatment for diabetic nephropathy

Wu, Yanqing; Li, Yi-Yang; Jiang, Ting; Yuan, Yuan; Li, Rui; Xu, Zeping; Zhong, Xingfeng; Ge, Jia; Liu, Yanlong; Xie, Ling; Xu, Ke; Zhang, Hongyu; Li, Xiaokun; Xiao, Jian

doi:10.1111/jcmm.13921

Cited by 20 publications

(20 citation statements)

References 35 publications

(85 reference statements)

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“…The db/db mice were divided into two groups and were intraperitoneally (i.p.) injected either with FGF1 (Guang et al, 2018) (0.5 mg/kg body weight, n = 8) or physiologic saline (n = 8) every other day for 4 weeks (Wu et al, 2018). After 4 weeks, body weights were measured.…”

Section: Animal Experimentsmentioning

confidence: 99%

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy

Wang

et al. 2020

Front. Pharmacol.

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Background: Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown. Methods: To further investigate the effect of FGF1 on diabetic liver injury, we divided db/ db mice into two groups and intraperitoneally (i.p.) injected either with FGF1 at 0.5 mg/kg body weight or saline every other day for 4 weeks. Then body weights were measured. Serum and liver tissues were collected for biochemical and molecular analyses. Results: FGF1 significantly reduced blood glucose and ameliorated diabetes-induced liver steatosis, fibrosis, and apoptosis. FGF1 also restored defective hepatic autophagy in db/db mice. Mechanistic investigations showed that diabetes markedly induced oxidative stress and endoplasmic reticulum stress and that FGF1 treatment significantly attenuated these effects. Conclusions: FGF1-associated glucose level reduction and amelioration of cellular stress are potential protective effects of FGF1 against diabetes-induced liver injury.

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Section: Animal Experimentsmentioning

confidence: 99%

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy

Wang

et al. 2020

Front. Pharmacol.

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“…Hyperglycemia with resulting elevated cellular stress is the major mediator of diabetes-associated onset of complications ( Wu et al, 2015 , 2018 ). Multiple studies have shown that the induction of ER stress is responsible for the pathogenetic progression of diabetes-associated neuropathy ( Lupachyk et al, 2013 ; Zhang et al, 2013 ; Wu et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline

Yuan

et al. 2020

Front. Cell Dev. Biol.

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Diabetes significantly induces cognitive dysfunction. Neuronal apoptosis is the main cause of diabetes-induced cognitive decline (DICD). Apoptosis signal-regulating kinase 1 (ASK1) and endoplasmic reticulum (ER) stress are remarkably activated by diabetes. The role and relationship of ASK1-JNK1/2 signaling and ER stress in DICD have not yet been elucidated. In this study, we used db/db mice as the DICD animal model and confirmed that db/db mice displayed cognitive decline with inferior learning and memory function. Diabetes significantly induced morphological and structural changes, excessive neuronal apoptosis, Aβ 1−42 large deposition, and synaptic dysfunction in the hippocampus. Mechanistic studies found that diabetes significantly triggered ASK1-JNK1/2 signaling activation and increased ER stress in the hippocampus. Moreover, diabetes enhanced the formation of the IRE1α-TRAF2-ASK1 complex, which promotes the crosstalk of ER stress and the ASK1-JNK1/2 pathway during DICD. Furthermore, 4-PBA treatment blocked high glucose (HG)-induced ASK1-JNK1/2 signaling activation, and excessive apoptosis in vitro. Inhibiting ASK1 via siRNA remarkably ameliorated the HG-induced increase in p-IRE1α and associated apoptosis in SH-SY5Y cells, suggesting that ASK1 is essential for the assembly and function of the proapoptotic kinase activity of the IRE1α signalosome. In summary, ER stress and ASK1-JNK1/2 signaling play causal roles in DICD development, which has crosstalk through the formation of the IRE1α-TRAF2-ASK1 complex.

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“…Nrf2 is a critical transcription factor to maintain redox homeostasis and regulates the expression of antioxidative stress genes including NQO1 and SODs (Dodson et al, 2019). It has been reported that hyperglycemia can induce oxidative stress and increase kidney injure via Nrf2 signaling (Wu et al, 2018). However, interestingly, our results show that bFGF treatment corrected the decreased levels of Nrf2, NQO1, and SOD2 in the kidney of db/db mice.…”

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confidence: 44%

The Protective Effect of Basic Fibroblast Growth Factor on Diabetic Nephropathy Through Remodeling Metabolic Phenotype and Suppressing Oxidative Stress in Mice

et al. 2020

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Diabetic nephropathy is a common complication in diabetes, but still lack of effective therapeutic strategies. This study aimed to investigate the therapeutic effect of basic fibroblast growth factor (bFGF) in db/db mice with diabetic nephropathy and explore its possible metabolic mechanisms using a nuclear magnetic resonance-based metabolomic approach. We found that bFGF treatment significantly alleviate urinary albumin to creatinine ratio and renal fibrosis in db/db mice, suggesting a potential renal protective effect. Metabolomics results reveal that bFGF remodeled metabolic phenotypes of the kidney and urine in db/db mice, mainly involving energy metabolism, methylamine metabolism, osmoregulation, and oxidative stress. Furthermore, the results show that bFGF-induced reductions of oxidative stress and apoptosis in db/db mice might be mediated by NOX-ROS-Nrf2 signaling. Therefore, our study suggests that the protective effect of bFGF on diabetic nephropathy could be mediated by remodeling metabolic phenotype and suppressing oxidative stress.

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Reduction of cellular stress is essential for Fibroblast growth factor 1 treatment for diabetic nephropathy

Cited by 20 publications

References 35 publications

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy

The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline

The Protective Effect of Basic Fibroblast Growth Factor on Diabetic Nephropathy Through Remodeling Metabolic Phenotype and Suppressing Oxidative Stress in Mice

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