Kidney fibrosis: from mechanisms to therapeutic medicines

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 17, 2023

Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.

Language: Английский

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Cisplatin nephrotoxicity: new insights and therapeutic implications

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 19(1), P. 53 - 72

Published: Oct. 13, 2022

Language: Английский

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H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 461, P. 132582 - 132582

Published: Sept. 19, 2023

Language: Английский

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Tubular cell senescence promotes maladaptive kidney repair and chronic kidney disease after cisplatin nephrotoxicity

JCI Insight, Journal Year: 2023, Volume and Issue: 8(8)

Published: March 14, 2023

Cisplatin is a widely used chemotherapy drug but it induces both acute and chronic kidney diseases (CKD) in cancer patients. The pathogenesis of cisplatin-induced CKD unclear effective renoprotective approaches are not available. Here, we report that repeated low-dose cisplatin (RLDC) treatment C57BL/6 mice induced cellular senescence tubules, accompanied with tubular degeneration pro-fibrotic phenotype transformation culminated maladaptive repair renal fibrosis. Suppression by senolytic drugs ABT-263 Fisetin attenuated fibrosis improved as indicated restoration regeneration function. In vitro, RLDC also mouse proximal BUMPT cells. eliminated senescent cells following treatment, reversed the increased their clonogenic activity. Moreover, alleviated paracrine effect RLDC-treated on fibroblasts for Consistently, knockdown p16 suppressed post-RLDC fibrotic changes cells, effects fibroblast proliferation. These results indicate persistent induction plays an important role promoting CKD. Targeting may be efficient to improve prevention

Language: Английский

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HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 25, 2023

Abstract Renal tubular epithelial cells (TECs) play a key role in kidney fibrosis by mediating cycle arrest at G2/M. However, the HDAC isoforms and underlying mechanism that are involved G2/M of TECs remain unclear. Here, we find Hdac9 expression is significantly induced mouse fibrotic kidneys, especially proximal tubules, aristolochic acid nephropathy (AAN) or unilateral ureter obstruction (UUO). Tubule-specific deletion HDAC9 pharmacological inhibition TMP195 attenuates cell G2/M, then reduces production profibrotic cytokine alleviates tubulointerstitial male mice. In vitro, knockdown loss phenotype fibroblasts activation through inhibiting Mechanistically, deacetylates STAT1 promotes its reactivation, followed inducing TECs, finally leading to fibrosis. Collectively, our studies indicate may be an attractive therapeutic target for

Language: Английский

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Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition

Metabolism, Journal Year: 2023, Volume and Issue: 145, P. 155592 - 155592

Published: May 23, 2023

Language: Английский

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Rodent models of AKI and AKI-CKD transition: an update in 2024

AJP Renal Physiology, Journal Year: 2024, Volume and Issue: 326(4), P. F563 - F583

Published: Feb. 1, 2024

Despite known drawbacks, rodent models are essential tools in the research of renal development, physiology, and pathogenesis. In past decade, have been developed used to mimic different etiologies acute kidney injury (AKI), AKI chronic disease (CKD) transition or progression, with comorbidities. These applied for both mechanistic preclinical drug development. However, current their limitations, especially since they often do not fully recapitulate pathophysiology human patients, thus need further refinement. Here, we discuss present status these models, including pathophysiologic compatibility, clinical translational significance, key factors affecting model consistency, main limitations. Future efforts should focus on establishing robust that simulate major molecular phenotypes its progression.

Language: Английский

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The role of epithelial cells in fibrosis: Mechanisms and treatment

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107144 - 107144

Published: March 13, 2024

Fibrosis is a pathological process that affects multiple organs and considered one of the major causes morbidity mortality in diseases, resulting an enormous disease burden. Current studies have focused on fibroblasts myofibroblasts, which directly lead to imbalance generation degradation extracellular matrix (ECM). In recent years, increasing number role epithelial cells fibrosis. some cases, are first exposed external physicochemical stimuli may drive collagen accumulation mesenchyme. other source stimulation mainly immune cytokines, similarly altered process. this review, we will focus dynamic alterations involved after injury during fibrogenesis, discuss association among them, summarize therapies targeting changed cells. Especially, mesenchymal transition (EMT) key central step, closely linked biological behaviors. Meanwhile, think disruption barrier, cell death basal stem populations stemness fibrosis not appreciated. We believe targeted can prevent progress fibrosis, but reverse it. The provide wonderful preventive delaying action.

Language: Английский

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Activation of lipophagy is required for RAB7 to regulate ferroptosis in sepsis-induced acute kidney injury

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 218, P. 120 - 131

Published: April 5, 2024

Language: Английский

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Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 29, 2024

Autophagy is a dynamic self-renovation biological process that maintains cell homeostasis and responsible for the quality control of proteins, organelles, energy metabolism. The E1-like ubiquitin-activating enzyme autophagy-related gene 7 (ATG7) critical factor initiates classic autophagy reactions by promoting formation extension autophagosome membranes. Recent studies have identified key functions ATG7 in regulating cycle, apoptosis, metabolism associated with occurrence development multiple diseases. This review summarizes how precisely programmed genetic, transcriptional, epigenetic modifications cells relationship between aging-related

Language: Английский

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