Wang Wei-Gang, Sun Wei-Xia, Gao Bao-Shan, Lian Xin, Zhou Hong-Lan
Department of Urology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021. China.
Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021. China.
Curr Protein Pept Sci. 2017;18(12):1224-1231. doi: 10.2174/1389203717666160915162238.
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.
目前对急性肾损伤（AKI）发病机制缺乏全面了解，这是其早期诊断和治疗的重大障碍。细胞周期停滞在急性肾损伤后肾小管上皮细胞的保护和适应性不良修复中起重要作用。G1期细胞停滞是急性肾损伤后的一种保护机制，可避免受损DNA的复制。胰岛素样生长因子结合蛋白7（IGFBP7）和金属蛋白酶组织抑制剂2（TIMP-2）在细胞损伤的极早期与G1细胞周期停滞密切相关，可作为预测急性肾损伤的理想生物标志物。然而，严重急性肾损伤后持续的细胞周期停滞可能导致细胞衰老和适应性不良修复，具有在间隙2（G2）或有丝分裂（M）期发生细胞周期停滞的典型特征。细胞周期停滞信号以自分泌或旁分泌方式从损伤部位向相邻细胞传递“警报”，导致促纤维化因子异常扩增和释放，周细胞/血管周围成纤维细胞活化，最终导致纤维化。因此，细胞周期调控已成为急性肾损伤防治的潜在新靶点。在本综述中，我们总结了急性肾损伤后细胞周期的特征以及能够早期检测急性肾损伤的细胞周期停滞标志物。我们还讨论了如何通过调节细胞周期停滞来预防慢性肾脏病（CKD）的进展。
