Oxidative RNA Damage in the Pathogenesis and Treatment of Type 2 Diabetes

Chen, Xiatian; Yu, Hua; Li, Zhe; Ye, Wei; Liu, Ziqian; Gao, Jinling; Wang, Yin; Li, Xin; Zhang, Lei; Alenina, Natalia; Bäder, Michael; Ding, Hongyan; Li, Peifeng; Aung, Lynn Htet Htet

doi:10.3389/fphys.2022.725919

Cited by 12 publications

(10 citation statements)

References 140 publications

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“…In fact, RNA oxidation is thought to play an important regulatory role in biological systems ( Tanaka and Chock, 2021 ). Oxidative modifications of various RNA forms have been demonstrated to occur under different pathological conditions, such as inflammation or metabolic dysregulation ( Fimognari, 2015 ; Liu et al, 2020 ; Chen et al, 2022 ). Furthermore, due to its impact on translation efficiency, where inhibiting actions have been reported ( Sochacka et al, 2015 ; Willi et al, 2018 ; Thomas et al, 2019 ), RNA oxidation may interfere with local protein synthesis related to homeostatic synaptic plasticity ( Coyle and Puttfarcken, 1993 ; Nunomura et al, 1999 ; for references to the role of local protein synthesis in homeostatic synaptic plasticity see Sutton et al, 2004 , 2006 ; Schuman et al, 2006 ; Sun et al, 2021 ; Kruse et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion

Lenz

Eichler

Kruse

et al. 2023

Front. Mol. Neurosci.

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Structural, functional, and molecular reorganization of denervated neural networks is often observed in neurological conditions. The loss of input is accompanied by homeostatic synaptic adaptations, which can affect the reorganization process. A major challenge of denervation-induced homeostatic plasticity operating in complex neural networks is the specialization of neuronal inputs. It remains unclear whether neurons respond similarly to the loss of distinct inputs. Here, we used in vitro entorhinal cortex lesion (ECL) and Schaffer collateral lesion (SCL) in mouse organotypic entorhino-hippocampal tissue cultures to study denervation-induced plasticity of CA1 pyramidal neurons. We observed microglia accumulation, presynaptic bouton degeneration, and a reduction in dendritic spine numbers in the denervated layers 3 days after SCL and ECL. Transcriptome analysis of the CA1 region revealed complex changes in differential gene expression following SCL and ECL compared to non-lesioned controls with a specific enrichment of differentially expressed synapse-related genes observed after ECL. Consistent with this finding, denervation-induced homeostatic plasticity of excitatory synapses was observed 3 days after ECL but not after SCL. Chemogenetic silencing of the EC but not CA3 confirmed the pathway-specific induction of homeostatic synaptic plasticity in CA1. Additionally, increased RNA oxidation was observed after SCL and ECL. These results reveal important commonalities and differences between distinct pathway lesions and demonstrate a pathway-specific induction of denervation-induced homeostatic synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion

Lenz

Eichler

Kruse

et al. 2023

Front. Mol. Neurosci.

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“…Diabetic kidney disease (DKD) is the main cause of end-stage renal disease globally (Nomura et al, 2021). It is a complex Frontiers in Physiology frontiersin.org disease process and involves many pathophysiologic mechanisms such as oxidative stress, inflammation and renal tubular injury caused by hyperglycemia, which eventually leads to renal fibrosis (Chen et al, 2022;Jung and Yoo, 2022). In this study, we first measured the stiffness of kidney tissues of DKD rats at different fibrosis stages (normal, 8 and 16 weeks after DKD), then successfully made an in vitro PA gel system consistent with the stiffness of kidneys in DKD rats in vivo by adjusting the ratio of AM and MBA, and finally determined the stiffness of 3 kPa, 12 kPa and 30 kPa to simulate the kidney stiffness in normal, DKD-8W and DKD-16W rats respectively.…”

Section: Discussionmentioning

confidence: 99%

Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation

Feng

Chen

et al. 2022

Front. Physiol.

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The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.

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“…There are abundant evidence-based reports that implicate the role of oxidative stress in the pathogenesis and/or progression of diabetic Mellitus in terms of glycemic control. 31 Increased glucose uptake in both skeletal muscle and adipose tissues enhances ROS generation and oxidative stress which in turn impairs glucose uptake and glycogen synthesis.…”

Section: Effects Of the Antioxidant Components Of Natural Honey On Gl...mentioning

confidence: 99%

The role of honey in the treatment of type 2 diabetes mellitus: a review of literature

Ofor

Erejuwa²,

Akuodor³

et al. 2022

Int J Basic Clin Pharmacol

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The use of honey in the control of hyperglycemia in patients with type 2 diabetes mellitus is a current option being explored globally. Honey bees which are named in Latin as Apis, use the collected nectar from plants to produce honey after regurgitation and digestion of nectar. Carbohydrate constitutes about 80% of the components of honey. It includes monosaccharides [fructose (37.5%) and glucose (30.6%), disaccharides (sucrose (1.6%) and maltose (2.7%)] and oligosaccharides. Natural honey also contains water (17.2%), proteins, vitamins, minerals, enzymes, acids such as flavonoids, phenolic acids and other components. Honey is rich in antioxidant content and these antioxidant compounds function as endogenous cellular antioxidant defences against free radicals in diabetes mellitus. Antioxidants have also been shown to exert a beneficial effects on blood glucose. Fructose and other bioactive constituents of honey have also been linked with amelioration of hyperglycemia. Besides the beneficial effects of honey on blood glucose, honey is widely used in the management of diabetic foot ulcers, an important complication of diabetes mellitus. The wound-healing benefits of honey are attributed to its antioxidant constituents and broad-spectrum antimicrobial activity. Though additional studies are needed, the use of honey in the management of diabetes mellitus holds much promise.

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Oxidative RNA Damage in the Pathogenesis and Treatment of Type 2 Diabetes

Cited by 12 publications

References 140 publications

Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion

Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion

Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation

The role of honey in the treatment of type 2 diabetes mellitus: a review of literature

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