Cell Cycle Arrest as a Therapeutic Target of Acute Kidney Injury

Author(s): Wei-gang Wang, Wei-xia Sun, Bao-shan Gao, Xin Lian, Hong-lan Zhou*.

Journal Name: Current Protein & Peptide Science

Volume 18 , Issue 12 , 2017

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Abstract:

The current lack of complete understanding of the pathogenesis of acute kidney injury (AKI) is a significant barrier to its early diagnosis and treatment. Cell cycle arrest plays an important role in the protection of renal tubular epithelial cells and maladaptive repair following AKI. G1 phase cell arrest serves as a protective mechanism following AKI, avoiding replication of damaged DNA. Insulinlike growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) are closely associated with G1 cell cycle arrest during the very early phase of cellular damage and can serve as an ideal biomarker to predict AKI. However, sustained cell cycle arrest after severe AKI may result in cell senescence and maladaptive repair, with typical characteristics of the development of cell cycle arrest in the gap 2 (G2) or mitotic (M) phase. Markers of cell cycle arrest signal and spread the “alarm” from the site of injury to adjacent cells in an autocrine or paracrine manner, giving rise to abnormal amplification and release of profibrogenic factors, activation of pericytes/perivascular fibroblasts, and eventually fibrosis. Therefore, cell cycle regulation has become a potentially new target for the prevention and treatment of AKI. In this review, we summarize the characteristics of the cell cycle following AKI and the markers of cell cycle arrest that enable the early detection of AKI. We also discuss how to prevent the progression of chronic kidney disease (CKD) by regulating cell cycle arrest.

Keywords: Acute kidney injury, cell cycle arrest, insulin-like growth factor-binding protein 7, tissue inhibitor of metalloproteinase- 2, pathogenesis, diagnosis.

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Article Details

VOLUME: 18
ISSUE: 12
Year: 2017
Page: [1224 - 1231]
Pages: 8
DOI: 10.2174/1389203717666160915162238
Price: $58

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