Wu Yun-Shan, Liang Shan, Li Dong-Yi, Wen Jun-Hao, Tang Ji-Xin, Liu Hua-Feng
Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Shunde Women and Children's Hospital, Guangdong Medical University (Foshan Shunde Maternal and Child Healthcare Hospital), Foshan, China.
Front Cell Dev Biol. 2021 Nov 25;9:714320. doi: 10.3389/fcell.2021.714320. eCollection 2021.
Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration. However, more severe or repeated injuries will lead to maladaptive repair, manifesting as cell cycle arrest or overproliferation of renal cells, both of which are closely related to renal fibrosis. Thus, cell cycle dysregulation of renal cells is a potential therapeutic target for the treatment of renal fibrosis. In this review, we focus on cell cycle regulation of renal cells in healthy and diseased kidney, discussing the role of cell cycle dysregulation of renal cells in renal fibrosis. Better understanding of the function of cell cycle dysregulation in renal fibrosis is essential for the development of therapeutics to halt renal fibrosis progression or promote regression.
细胞周期的精确调控对于组织稳态和发育至关重要，而细胞周期失调与许多人类疾病相关，包括肾纤维化，这是各种慢性肾脏病进展至终末期肾病的常见过程。在正常生理条件下，大多数肾细胞是处于细胞周期G0期的有丝分裂后静止细胞，肾细胞更新率非常低。毒素、缺氧和代谢紊乱引起的损伤可刺激肾细胞进入细胞周期，这对于肾脏再生和肾功能恢复至关重要。然而，更严重或反复的损伤会导致适应性修复不良，表现为肾细胞的细胞周期停滞或过度增殖，这两者均与肾纤维化密切相关。因此，肾细胞的细胞周期失调是治疗肾纤维化的潜在治疗靶点。在本综述中，我们聚焦于健康和患病肾脏中肾细胞的细胞周期调控，探讨肾细胞周期失调在肾纤维化中的作用。更好地理解细胞周期失调在肾纤维化中的功能对于开发阻止肾纤维化进展或促进其逆转的治疗方法至关重要。
