Cellular senescence of renal tubular epithelial cells in renal fibrosis

Zhang, Junqing; Li, Yingying; Zhang, Xueyan; Tian, Zenghui; Liu, Cheng; Wang, Shitao; Zhang, Farong

doi:10.3389/fendo.2023.1085605

Cited by 15 publications

(18 citation statements)

References 113 publications

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“…There is a rising prevalence of glomerulosclerosis and interstitial fibrosis in the aging kidney. Similarly, chronic accumulation of multiple senescent cells in renal diseases can also contribute to progressive renal fibrosis after injury [ 64 , 65 ].…”

Section: Roles Of P53 In Organ Fibrosismentioning

confidence: 99%

Targeting tumor suppressor p53 for organ fibrosis therapy

Bao,

Yang,

Shen

et al. 2024

Cell Death Dis

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Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53’s relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

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Section: Roles Of P53 In Organ Fibrosismentioning

confidence: 99%

Targeting tumor suppressor p53 for organ fibrosis therapy

Bao,

Yang,

Shen

et al. 2024

Cell Death Dis

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“…Upregulation of NRF2 has been suggested as a mechanism for reduced cellular senescence in models of diseases such as osteoporosis [ 180 ], age-related macular degeneration [ 181 ], age-related cognitive decline [ 182 ] and renal fibrosis [ 183 ]. Recently, Liu et al described how NRF2 is activated during DOX-induced senescence in two human cancer cell lines and in vivo by an accumulation of the oncogene iASPP (Inhibitor of Apoptosis Stimulating Protein of P53), which binds and inhibits KEAP1 [ 184 , 185 ].…”

Section: Drug-induced Cardiotoxicity and The Role Of Nrf2mentioning

confidence: 99%

Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling

Roberts

Rainbow

Sharma

2023

IJMS

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Cardiovascular toxicity and diseases are phenomena that have a vastly detrimental impact on morbidity and mortality. The pathophysiology driving the development of these conditions is multifactorial but commonly includes the perturbance of reactive oxygen species (ROS) signalling, iron homeostasis and mitochondrial bioenergetics. The transcription factor nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2), a master regulator of cytoprotective responses, drives the expression of genes that provide resistance to oxidative, electrophilic and xenobiotic stresses. Recent research has suggested that stimulation of the NRF2 signalling pathway can alleviate cardiotoxicity and hallmarks of cardiovascular disease progression. However, dysregulation of NRF2 dynamic responses can be severely impacted by ageing processes and off-target toxicity from clinical medicines including anthracycline chemotherapeutics, rendering cells of the cardiovascular system susceptible to toxicity and subsequent tissue dysfunction. This review addresses the current understanding of NRF2 mechanisms under homeostatic and cardiovascular pathophysiological conditions within the context of wider implications for this diverse transcription factor.

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“…Recent reports showed senescent cells greatly accumulate in kidneys in various CKDs 7,8 . Cell senescence in tubular cells is an early event in renal fibrosis and is highly associated with the progression of disease 9,10 . Cell senescence is driven by the activation of p53, p21 as well as P16 INK4A , with a phenotype of permanent cell cycle arrest.…”

Section: Introductionmentioning

confidence: 99%

C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

Wu,

Chen,

et al. 2024

J Cellular Molecular Medi

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The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis is a common pathological feature in various CKD. Previous studies showed tubular cell senescence is highly involved in the pathogenesis of renal fibrosis. However, the inducers of tubular senescence and the underlying mechanisms have not been fully investigated. C‐X‐C motif chemokine receptor 4 (CXCR4), a G‐protein‐coupled seven‐span transmembrane receptor, increases renal fibrosis and plays an important role in tubular cell injury. Whereas, whether CXCR4 could induce tubular cell senescence and the detailed mechanisms have not studied yet. In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line. Overexpression or knockdown of CXCR4 was obtained by injection of related plasmids. We identified CXCR4 increased in injury tubular cells. CXCR4 was expressed predominantly in renal tubular epithelial cells and co‐localized with adipose differentiation‐related protein (ADRP) as well as the senescence‐related protein P16INK4A. Furthermore, we found overexpression of CXCR4 greatly induced the activation of β‐catenin, while knockdown of CXCR4 inhibited it. We also found that CXCR4 inhibited fatty acid oxidation and triggered lipid deposition in tubular cells. To inhibit β‐catenin by ICG‐001, an inhibitor of β‐catenin, could significantly block CXCR4‐suppressed fatty acid oxidation. Taken together, our results indicate that CXCR4 is a key mediator in tubular cell senescence and renal fibrosis. CXCR4 promotes tubular cell senescence and renal fibrosis by inducing β‐catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.

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Cellular senescence of renal tubular epithelial cells in renal fibrosis

Cited by 15 publications

References 113 publications

Targeting tumor suppressor p53 for organ fibrosis therapy

Targeting tumor suppressor p53 for organ fibrosis therapy

Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling

C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

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