scholarly journals SARS‐CoV‐2 N Protein Induces Acute Kidney Injury via Smad3‐Dependent G1 Cell Cycle Arrest Mechanism

2021 ◽  
pp. 2103248
Author(s):  
Wenbiao Wang ◽  
Junzhe Chen ◽  
Dingwen Hu ◽  
Pan Pan ◽  
Liying Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Cell Cycle Arrest ◽  
Kidney Injury ◽  
N Protein ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

Smad7 protects against acute kidney injury by rescuing tubular epithelial cells from the G1 cell cycle arrest

2017 ◽  
Vol 131 (15) ◽  
pp. 1955-1969 ◽  
Author(s):  
Sha Fu ◽  
Ying Tang ◽  
Xiao R. Huang ◽  
Min Feng ◽  
An P. Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Cyclin E ◽  
Kidney Injury ◽  
Protective Role ◽  
Tubular Epithelial Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here, we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI. In contrast, restored renal Smad7 gene locally into the kidney of Smad7 KO mice protected against AKI by promoting TEC proliferation identified by PCNA+ and BrdU+ cells. Mechanistic studies revealed that worsen AKI in Smad7 KO mice was associated with a marked activation of TGF-β/Smad3-p21/p27 signaling and a loss of CDK2/cyclin E activities, thereby impairing TEC regeneration at the G1 cell cycle arrest. In contrast, restored Smad7 locally into the kidneys of Smad7 KO mice protected TECs from the G1 cell cycle arrest and promoted TEC G1/S transition via a CDK2/cyclin E-dependent mechanism. In conclusion, Smad7 plays a protective role in AKI. Blockade of TGF-β/Smad3-p21/p27-induced G1 cell cycle arrest may be a key mechanism by which Smad7 treatment inhibits AKI. Thus, Smad7 may be a novel therapeutic agent for AKI.

scholarly journals Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Critical Care ◽  
2013 ◽  
Vol 17 (1) ◽  
pp. R25 ◽  
Author(s):  
Kianoush Kashani ◽  
Ali Al-Khafaji ◽  
Thomas Ardiles ◽  
Antonio Artigas ◽  
Sean M Bagshaw ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Cell Cycle Arrest ◽  
Kidney Injury ◽  
Cycle Arrest

Improving clinical prediction rules in acute kidney injury with the use of biomarkers of cell cycle arrest: a pilot study

Biomarkers ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Luke E. Hodgson ◽  
Richard M. Venn ◽  
Steve Short ◽  
Paul J. Roderick ◽  
Duncan Hargreaves ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Pilot Study ◽  
Cell Cycle Arrest ◽  
Kidney Injury ◽  
Clinical Prediction ◽  
Clinical Prediction Rules ◽  
Prediction Rules ◽  
Cycle Arrest

scholarly journals Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury after Pediatric Cardiac Surgery

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110865 ◽  
Author(s):  
Melanie Meersch ◽  
Christoph Schmidt ◽  
Hugo Van Aken ◽  
Jan Rossaint ◽  
Dennis Görlich ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Cell Cycle Arrest ◽  
Kidney Injury ◽  
Pediatric Cardiac Surgery ◽  
Cycle Arrest
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