7-Hydroxycoumarin Protects Against Cisplatin-Induced Acute Kidney Injury by Inhibiting RIPK1/RIPK3/MLKL-Mediated Necroptosis and Promoting Sox-9-Mediated Tubular Epithelial Cell Proliferation

2019 ◽  
Author(s):  
Wei-Feng Wu ◽  
Jia-Nan Wang ◽  
Zeng Li ◽  
Biao Wei ◽  
Juan Jin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Kidney Injury ◽  
Epithelial Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Proliferation

Cyclin kinase inhibitor p21CIP1/WAF1 limits interstitial cell proliferation following ureteric obstruction

1999 ◽  
Vol 277 (6) ◽  
pp. F948-F956 ◽  
Author(s):  
Jeremy Hughes ◽  
Paul Brown ◽  
Stuart J. Shankland
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Interstitial Cell ◽  
Tubular Epithelial Cell ◽  
Collagen I ◽  
Macrophage Infiltration ◽  
Nuclear Antigen ◽  
Epithelial Cell Proliferation ◽  
Ureteric Obstruction ◽  
Proliferation And Apoptosis

Tubulointerstitial renal injury induced by unilateral ureteric obstruction (UUO) is characterized by marked cell proliferation and apoptosis. Proliferation requires cell cycle transit that is positively regulated by cyclins and cyclin-dependent kinases (CDKs) and inhibited by the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs: p21, p27, and p57). We have shown that the absence of p27 results in markedly increased tubular epithelial cell proliferation and apoptosis following UUO (V. Ophascharoensuk, M. L. Fero, J. Hughes, J. M. Roberts, and S. J. Shankland. Nat. Med.4: 575–580, 1998). Since p21 mRNA is upregulated following UUO, we hypothesized that p21 would also serve to limit cell proliferation and apoptosis. We performed UUO in p21 +/+ and p21 −/− mice. Cell proliferation [bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA)], apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method], interstitial myofibroblast accumulation (actin), macrophage infiltration (F4/80), and collagen I expression were quantified at days 3, 7, and 14. In contrast to p27 −/− mice, there was no difference in tubular epithelial cell proliferation or apoptosis between p21 −/− and p21 +/+ mice at any time point. However, interstitial cell proliferation at day 3 was significantly increased in p21 −/− mice [BrdU, 40.7 ± 1.9 cells/high-power field (cells/hpf) vs. 28.8 ± 2, P< 0.005], although, interestingly, no difference was seen in interstitial cell apoptosis. Actin/BrdU double staining demonstrated increased interstitial myofibroblast proliferation at day 3 in p21 −/− animals (10 ± 0.12 vs. 5.8 ± 0.11 cells/hpf, P < 0.05), which was followed by increased myofibroblast accumulation at day 7 in p21 −/− mice. No differences were detected in interstitial macrophage infiltration, collagen I deposition or transforming growth factor-β1 mRNA (in situ hybridization) expression. In conclusion p21, unlike p27, is not essential for the regulation of tubular epithelial cell proliferation and apoptosis following UUO, but p21 levels do serve to limit the magnitude of the early myofibroblast proliferation. This study demonstrates a differential role for the CKI p21 and p27 in this model.

scholarly journals MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury

2016 ◽  
Vol 7 (11) ◽  
pp. e2482-e2482 ◽  
Author(s):  
Dana Thomasova ◽  
Martrez Ebrahim ◽  
Kristina Fleckinger ◽  
Moying Li ◽  
Jakob Molnar ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Epithelial Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Death

scholarly journals Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury

2015 ◽  
Vol 8 (5) ◽  
pp. 548-559 ◽  
Author(s):  
Sandra M. Sancho-Martínez ◽  
José M. López-Novoa ◽  
Francisco J. López-Hernández
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Epithelial Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Pathophysiological Role ◽  
Epithelial Cell Death

The cleavage of gasdermin D by caspase-11 promotes tubular epithelial cell pyroptosis and urinary IL-18 excretion in acute kidney injury

2019 ◽  
Vol 96 (5) ◽  
pp. 1105-1120 ◽  
Author(s):  
Naijun Miao ◽  
Fan Yin ◽  
Hongyan Xie ◽  
Yanzhe Wang ◽  
Yiang Xu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Epithelial Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cell

scholarly journals USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Fei Gao ◽  
Mingjiang Qian ◽  
Guoyue Liu ◽  
Wanping Ao ◽  
Dahua Dai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Epithelial Cell ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Renal Tubular Epithelial Cell ◽  
Renal Tubular

Abstract Background Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. Results In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. Conclusions This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.

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