The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury

Zhou, Xun; Chen, Hui; Shi, Yingfeng; Ma, Xiaoyan; Zhuang, Songlin; Liu, Na

doi:10.3389/fphar.2021.695237

Cited by 9 publications

(10 citation statements)

References 88 publications

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“…There is evidence to indicate that HDACs have an important role in the pathophysiology of AKI through transcriptional regulation of various genes involved in apoptosis, inflammation, oxidative stress, ATP production, and fibrosis [81]. They regulate proinflammatory cytokine release, EGFR (epidermal growth factor receptor), TGF/Smad, NF-κB signaling, and cell cycle arrest [81]. Class I and II HDAC inhibitors are generally protective during experimental renal injury [71].…”

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

“…Class I and II HDAC inhibitors are generally protective during experimental renal injury [71]. However, class I HDAC inhibitors have exhibited mixed results in different AKI models, which may result from differences in the time course of tubular repair among AKI models, the structures of administered HDAC inhibitors, and the dose and timing of administration [81]. Class III HDACs, sirtuins, are expressed in different subcellular compartments and play different roles in cellular homeostasis.…”

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

“…Many studies have shown that sirtuins are involved in the pathogenesis of AKI through regulation of oxidative stress, apoptosis, inflammation, autophagy, and mitochondrial biogenesis. Overexpression of SIRT1, SIRT3, and SIRT6, and the suppression of SIRT7 and SIRT2 are renoprotective [81]. For class IV, HDAC11 gene silencing increased PAI-1 expression, which can induce inflammation and functional impairment following ischemic insult [82].…”

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

“…For class IV, HDAC11 gene silencing increased PAI-1 expression, which can induce inflammation and functional impairment following ischemic insult [82]. HDAC11 may represent a new therapeutic target for AKI [81].…”

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

“…Although a variety of HDAC inhibitors have been shown to exhibit anti-fibrotic and anti-inflammatory activity and effectiveness on various renal diseases in animal models [83], their application to human clinical trials has been limited because of their adverse effects, which include hyponatremia, hypokalemia, edema, and blood pressure changes [81,84]. To reduce toxicity and improve clinical efficacy, more specific HDAC inhibitors, rather than pan-HDAC inhibitors or class-specific HDAC inhibitors, need to be developed [81]. Moreover, the precise dosing for the desired effect, the proper timing of therapeutic intervention, and effective drug delivery should all be taken into account for clinical application.…”

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

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Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition

Tanemoto

Mimura

2022

Pharmaceuticals

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Acute kidney injury (AKI) was previously thought to be a merely transient event; however, recent epidemiological evidence supports the existence of a causal relationship between AKI episodes and subsequent progression to chronic kidney disease (CKD). Although the pathophysiology of this AKI-to-CKD transition is not fully understood, it is mediated by the interplay among multiple components of the kidney including tubular epithelial cells, endothelial cells, pericytes, inflammatory cells, and myofibroblasts. Epigenetic alterations including histone modification, DNA methylation, non-coding RNAs, and chromatin conformational changes, are also expected to be largely involved in the pathophysiology as a “memory” of the initial injury that can persist and predispose to chronic progression of fibrosis. Each epigenetic modification has a great potential as a therapeutic target of AKI-to-CKD transition; timely and target-specific epigenetic interventions to the various temporal stages of AKI-to-CKD transition will be the key to future therapeutic applications in clinical practice. This review elaborates on the latest knowledge of each mechanism and the currently available therapeutic agents that target epigenetic modification in the context of AKI-to-CKD transition. Further studies will elucidate more detailed mechanisms and novel therapeutic targets of AKI-to-CKD transition.

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Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

Section: • Hdac Inhibitors In Aki-to-ckd Transitionmentioning

confidence: 99%

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Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition

Tanemoto

Mimura

2022

Pharmaceuticals

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Nutrition and autophagy deficiency in critical illness

Vanhorebeek

Casaer

Gunst

2023

Current Opinion in Critical Care

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Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high risk of multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. This review discusses insight into the role of autophagy in critical illness and the involvement of artificial feeding in insufficient autophagy activation in critical illness. Recent findings Animal studies manipulating autophagy have shown its protective effects against kidney, lung, liver, and intestinal injury after several critical insults. Autophagy activation also protected peripheral, respiratory, and cardiac muscle function, despite aggravated muscle atrophy. Its role in acute brain injury is more equivocal. Animal and patient studies showed that artificial feeding suppressed autophagy activation in critical illness, particularly with high protein/amino acid doses. Feeding-suppressed autophagy may explain short and long-term harm by early enhanced calorie/protein feeding in large randomized controlled trials. Summary Insufficient autophagy during critical illness is at least partly explained by feeding-induced suppression. This may explain why early enhanced nutrition failed to benefit critically ill patients or even induced harm. Safe, specific activation of autophagy avoiding prolonged starvation opens perspectives for improving outcomes of critical illness.

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Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair

Wang,

Yu,

et al. 2024

J Cellular Molecular Medi

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Nephrotoxicity is a major side effect of platinum‐based antineoplastic drugs, and there is currently no available therapeutic intervention. Our study suggests that targeting histone deacetylase 8 could be a potential treatment for cisplatin‐induced acute kidney injury (AKI). In a murine model of AKI induced by cisplatin, the administration of PCI‐34051, a selective inhibitor of HDAC8, resulted in significant improvement in renal function and reduction in renal tubular damage and apoptosis. Pharmacological inhibition of HDAC8 also decreased caspase‐3 and PARP1 cleavage, attenuated Bax expression and preserved Bcl‐2 levels in the injured kidney. In cultured murine renal epithelial cells (mRTECs) exposed to cisplatin, treatment with PCI‐34051 or transfection with HDAC8 siRNA reduced apoptotic cell numbers and diminished expression of cleaved caspase‐3 and PARP1; conversely, overexpression of HDAC8 intensified these changes. Additionally, PCI‐34051 reduced p53 expression levels along with those for p21, p‐CDK2 and γ‐H2AX while preserving MRE11 expression in the injured kidney. Similarly, pharmacological and genetic inhibition of HDAC8 reduced γ‐H2AX and enhanced MRE11 expression; conversely, HDAC8 overexpression exacerbated these changes in mRTECs exposed to cisplatin. These results support that HDAC8 inhibition attenuates cisplatin‐induced AKI through a mechanism associated with reducing DNA damage and promoting its repair.

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The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury

Cited by 9 publications

References 88 publications

Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition

Therapies Targeting Epigenetic Alterations in Acute Kidney Injury-to-Chronic Kidney Disease Transition

Nutrition and autophagy deficiency in critical illness

Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair

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