Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Zhu, Zijing; Hu, Jijia; Chen, Zhaowei; Feng, Jun; Yang, Xueyan; Liang, Wei; Ding, Guohua

doi:10.1016/j.metabol.2022.155194

Cited by 72 publications

(41 citation statements)

References 141 publications

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“…Recent studies suggest “metabolic reprogramming” of tubular epithelial cells is also an important factor that contributes to the AKI-to-CKD transition ( Gomez et al, 2017 ; Zhu et al, 2022 ). As an adaptive response to hypoxic microenvironments, cancer cells shift energy sources from mitochondrial fatty acid β-oxidation (FAO) to glycolysis, which is known as the Warburg effect ( Sun et al, 2018 ; Zhu et al, 2022 ). As mentioned in the previous section, tubular epithelial cells have high energy demands rendering them susceptible to AKI.…”

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

“…This process is considered a protective process for surviving tubular epithelial cells during the repair phase of AKI; besides restoring ATP production, enhanced glycolysis following acute injury contributes to fibroblast activation by generating lactate (the final product of glycolysis), which may promote wound healing and tubular regeneration as a protective inflammatory response ( Gomez et al, 2017 ; Shen et al, 2020 ; Li et al, 2021 ). However, this metabolic reprogramming is a double-edged sword with respect to renal prognosis; the persistent shutdown of FAO and enhanced glycolysis in tubular epithelial cells contributes to the transition to CKD accompanied by chronic inflammation and lipid accumulation ( Schaub et al, 2021 ; Zhu et al, 2022 ). Kang et al showed that fibrotic kidneys from humans and mice exhibit lower expression of enzymes and regulators involved in FAO ( Kang et al, 2015 ).…”

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

“…In particular, they demonstrated that decreased FAO alone is sufficient to induce a phenotypic change that promotes fibrosis in tubular epithelial cells, whereas genetic or pharmacologic replenishment of FAO protects mice from kidney fibrosis ( Kang et al, 2015 ). Lipid accumulation in nonadipose tissue results in lipotoxicity, including cell dysfunction and necrosis ( Zhu et al, 2022 ). Decreased FAO results in the reduced use of free fatty acids in tubular epithelial cells, which promotes lipid accumulation and tubulointerstitial fibrosis ( Jang et al, 2020 ; Zhu et al, 2022 ).…”

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

“…Lipid accumulation in nonadipose tissue results in lipotoxicity, including cell dysfunction and necrosis ( Zhu et al, 2022 ). Decreased FAO results in the reduced use of free fatty acids in tubular epithelial cells, which promotes lipid accumulation and tubulointerstitial fibrosis ( Jang et al, 2020 ; Zhu et al, 2022 ).…”

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

“…Myofibroblasts are activated forms of fibroblasts that produce large amounts of extracellular matrix (ECM) that contributes to tissue fibrosis formation (Jun and Lau, 2018). These cells are predominantly derived from resident fibroblasts and pericytes (Kuppe et al, 2021) (other origins include bone marrow-derived macrophages (Tang et al, 2019;Chen J. et al, 2022) and endothelial-to-mesenchymal transition (Chen Y. et al, 2022)), and their function is influenced by profibrotic signals emanating from tubular cells and inflammatory cells (Ullah and Basile, 2019). Tubulointerstitial fibrosis aggravates renal hypoxia through further loss of capillaries and the increasing physical distance between resident tubular cells and capillaries.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition

Tanemoto

Nangaku

Mimura

2022

Front. Mol. Biosci.

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Epigenetic memory, which refers to the ability of cells to retain and transmit epigenetic marks to their daughter cells, maintains unique gene expression patterns. Establishing programmed epigenetic memory at each stage of development is required for cell differentiation. Moreover, accumulating evidence shows that epigenetic memory acquired in response to environmental stimuli may be associated with diverse diseases. In the field of kidney diseases, the “memory” of acute kidney injury (AKI) leads to progression to chronic kidney disease (CKD); epidemiological studies show that patients who recover from AKI are at high risk of developing CKD. The underlying pathological processes include nephron loss, maladaptive epithelial repair, inflammation, and endothelial injury with vascular rarefaction. Further, epigenetic alterations may contribute as well to the pathophysiology of this AKI-to-CKD transition. Epigenetic changes induced by AKI, which can be recorded in cells, exert long-term effects as epigenetic memory. Considering the latest findings on the molecular basis of epigenetic memory and the pathophysiology of AKI-to-CKD transition, we propose here that epigenetic memory contributing to AKI-to-CKD transition can be classified according to the presence or absence of persistent changes in the associated regulation of gene expression, which we designate “driving” memory and “priming” memory, respectively. “Driving” memory, which persistently alters the regulation of gene expression, may contribute to disease progression by activating fibrogenic genes or inhibiting renoprotective genes. This process may be involved in generating the proinflammatory and profibrotic phenotypes of maladaptively repaired tubular cells after kidney injury. “Priming” memory is stored in seemingly successfully repaired tubular cells in the absence of detectable persistent phenotypic changes, which may enhance a subsequent transcriptional response to the second stimulus. This type of memory may contribute to AKI-to-CKD transition through the cumulative effects of enhanced expression of profibrotic genes required for wound repair after recurrent AKI. Further understanding of epigenetic memory will identify therapeutic targets of future epigenetic intervention to prevent AKI-to-CKD transition.

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Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

Section: Update On the Pathophysiology Of Aki-to-ckd Transitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition

Tanemoto

Nangaku

Mimura

2022

Front. Mol. Biosci.

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Self‐Assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis

Xin,

Gong,

Chen

et al. 2024

Adv Healthcare Materials

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Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI was quite limited due to the low efficiency and poor kidney‐targeting ability. Herein, a novel self‐assembling peptide nanoparticle with specific p38‐inhibiting activity was constructed, which linked mitogen‐activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell‐penetrating TAT sequence, ultimately self‐assembling into TAT‐MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia‐reperfusion injury (IRI)‐induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis‐inducing capacity and synergistic potent antioxidant property in AKI. Our findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS‐scavenging and ferroptosis‐mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD.This article is protected by copyright. All rights reserved

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Tight junctions and acute kidney injury

Wei

Yang

et al. 2023

Journal Cellular Physiology

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Acute kidney injury (AKI) is characterized by a rapid reduction in kidney function caused by various etiologies. Tubular epithelial cell dysregulation plays a pivotal role in the pathogenesis of AKI. Tight junction (TJ) is the major molecular structure that connects adjacent epithelial cells and is critical in maintaining barrier function and determining the permeability of epithelia. TJ proteins are dysregulated in various types of AKI, and some reno‐protective drugs can reverse TJ changes caused by insult. An in‐depth understanding of TJ regulation and its causality with AKI will provide more insight to the disease pathogenesis and will shed light on the potential role of TJs to serve as novel therapeutic targets in AKI.

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Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Cited by 72 publications

References 141 publications

Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition

Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition

Self‐Assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis

Tight junctions and acute kidney injury

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