scholarly journals Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis

2014 ◽  
Vol 4 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Joseph V. Bonventre
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Proximal Tubule ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

scholarly journals CDK4/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury

2014 ◽  
Vol 306 (4) ◽  
pp. F379-F388 ◽  
Author(s):  
Derek P. DiRocco ◽  
John Bisi ◽  
Patrick Roberts ◽  
Jay Strum ◽  
Kwok-Kin Wong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Kidney Injury ◽  
Epithelial Cell ◽  
Proximal Tubule ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Kidney Injury ◽  
Epithelial Proliferation ◽  
Cycle Arrest

Acute kidney injury (AKI) is common and urgently requires new preventative therapies. Expression of a cyclin-dependent kinase (CDK) inhibitor transgene protects against AKI, suggesting that manipulating the tubular epithelial cell cycle may be a viable therapeutic strategy. Broad spectrum small molecule CDK inhibitors are protective in some kidney injury models, but these have toxicities and epithelial proliferation is eventually required for renal repair. Here, we tested a well-tolerated, novel and specific small molecule inhibitor of CDK4 and CDK6, PD 0332991, to investigate the effects of transient cell cycle inhibition on epithelial survival in vitro and kidney injury in vivo. We report that CDK4/6 inhibition induced G0/G1 cycle arrest in cultured human renal proximal tubule cells (hRPTC) at baseline and after injury. Induction of transient G0/G1 cycle arrest through CDK4/6 inhibition protected hRPTC from DNA damage and caspase 3/7 activation following exposure to the nephrotoxins cisplatin, etoposide, and antimycin A. In vivo, mice treated with PD 0332991 before ischemia-reperfusion injury (IRI) exhibited dramatically reduced epithelial progression through S phase 24 h after IRI. Despite reduced epithelial proliferation, PD 0332991 ameliorated kidney injury as reflected by improved serum creatinine and blood urea nitrogen levels 24 h after injury. Inflammatory markers and macrophage infiltration were significantly decreased in injured kidneys 3 days following IRI. These results indicate that induction of proximal tubule cell cycle arrest with specific CDK4/6 inhibitors, or “pharmacological quiescence,” represents a novel strategy to prevent AKI.

scholarly journals MicroRNA‐493 targets STMN‐1 and promotes hypoxia‐induced epithelial cell cycle arrest in G 2 /M and renal fibrosis

2018 ◽  
Vol 33 (2) ◽  
pp. 1565-1577 ◽  
Author(s):  
Ting Liu ◽  
Limin Liu ◽  
Minna Liu ◽  
Rui Du ◽  
Yangjie Dang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Cycle Arrest ◽  
Renal Fibrosis ◽  
Cycle Arrest

scholarly journals Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest

1999 ◽  
Vol 147 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Hongran Fan ◽  
Paul A. Khavari
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Cycle Arrest ◽  
Sonic Hedgehog ◽  
Growth Arrest ◽  
Epidermal Hyperplasia ◽  
Shh Pathway ◽  
Cycle Arrest ◽  
Pathway Activation

Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity. In addition, Shh blocks p21CIP1/WAF1-induced growth arrest. These data indicate that Shh promotes neoplasia by opposing normal stimuli for epithelial cell cycle arrest.

scholarly journals Maladaptive Proximal Tubule Repair: Cell Cycle Arrest

2014 ◽  
Vol 127 (1-4) ◽  
pp. 61-64 ◽  
Author(s):  
Joseph V. Bonventre
Keyword(s):  
Cell Cycle ◽  
Proximal Tubule ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

scholarly journals Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury

2010 ◽  
Vol 16 (5) ◽  
pp. 535-543 ◽  
Author(s):  
Li Yang ◽  
Tatiana Y Besschetnova ◽  
Craig R Brooks ◽  
Jagesh V Shah ◽  
Joseph V Bonventre
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Cycle Arrest ◽  
Kidney Fibrosis ◽  
Cycle Arrest

Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest*

2003 ◽  
Vol 31 (6) ◽  
pp. 1630-1637 ◽  
Author(s):  
Craig M. Coopersmith ◽  
Paul E. Stromberg ◽  
Christopher G. Davis ◽  
W. Michael Dunne ◽  
Daniel M. Amiot ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pseudomonas Aeruginosa ◽  
Epithelial Cell ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Intestinal Proliferation

scholarly journals Retinoblastoma protein promotes uterine epithelial cell cycle arrest and necroptosis for embryo invasion

EMBO Reports ◽  
2021 ◽  
Author(s):  
Shun Akaeda ◽  
Yasushi Hirota ◽  
Yamato Fukui ◽  
Shizu Aikawa ◽  
Ryoko Shimizu‐Hirota ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Cycle Arrest ◽  
Retinoblastoma Protein ◽  
Uterine Epithelial Cell ◽  
Cycle Arrest
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