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 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.

Mechanisms of cadmium (Cd 2+ ) induced G2 phase cell cycle arrest in renal proximal tubule (PT) cells

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Ulrich Bork ◽  
Wing‐Kee Lee ◽  
Thomas Dittmar ◽  
Frank Thévenod
Keyword(s):  
Cell Cycle ◽  
Proximal Tubule ◽  
Cell Cycle Arrest ◽  
Renal Proximal Tubule ◽  
Phase Cell ◽  
Cycle Arrest ◽  
G2 Phase

Proximal tubule cyclophilin D mediates kidney fibrogenesis in obstructive nephropathy

2021 ◽  
Author(s):  
Hee-Seong Jang ◽  
Mi Ra Noh ◽  
Ligyeom Ha ◽  
Jinu Kim ◽  
Babu J. Padanilam
Keyword(s):  
Cell Cycle ◽  
Proximal Tubule ◽  
Cell Cycle Arrest ◽  
Critical Factor ◽  
Acute Injury ◽  
Cyclophilin D ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Fibrosis Progression ◽  
Cycle Arrest

Proximal tubule (PT) is highly vulnerable to acute injury, including ischemic insult and nephrotoxins, and chronic kidney injury. It is established that PT injury is a primary cause of development of chronic kidney disease, but the underlying molecular mechanism remains to be defined. Here, we tested whether PT cyclophilin D (CypD), a mitochondrial matrix protein, is a critical factor to cause kidney fibrosis progression. To define the role of CypD in kidney fibrosis, we used an established mouse model for kidney fibrosis, unilateral ureteral obstruction (UUO) model in global and PT-specific CypD knockout (KO). Global CypD KO blunted kidney fibrosis progression with inhibition of myofibroblast activation and fibrosis. UUO-induced tubular atrophy was suppressed in kidneys of global CypD KO, but not tubular dilation or apoptotic cell death. PT cell cycle arrest was highly increased in WT-UUO kidneys, but markedly attenuated in global CypD KO-UUO kidneys. The number of macrophages and neutrophils was less in UUO kidneys of global CypD KO than those of WT. The pro-inflammatory and -fibrotic factors were all inhibited in global CypD KO. In line with those of global CypD KO, PT-specific CypD KO also blunted kidney fibrosis progression, along with less tubular atrophy, renal parenchymal loss, cell cycle arrest in PT and inflammation, indicating a critical role for PT CypD in fibrogenesis. Collectively, our data demonstrate that CypD in PT is a critical factor contributing to kidney fibrosis in UUO, providing a new paradigm for mitochondria-targeted therapeutics of fibrotic diseases.

Helicobacter pylori induces cell cycle arrest of T-lymphocytes

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Gerhard ◽  
C Schmees ◽  
R Rad ◽  
P Voland ◽  
T Treptau ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Helicobacter Pylori ◽  
T Lymphocytes ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

Mechanisms of interferon-induced cell cycle arrest

10.2741/a527 ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. d479-487 ◽  
Author(s):  
Dan Grandér
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest
Sign in / Sign up

Export Citation Format

Share Document