Khamchun Supaporn, Thongboonkerd Visith
1Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
2Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Cell Death Discov. 2018 Nov 21;4:106. doi: 10.1038/s41420-018-0123-9. eCollection 2018.
Renal tubular cell injury can enhance calcium oxalate monohydrate (COM) crystal adhesion at the injured site and thus may increase the stone risk. Nevertheless, underlying mechanism of such enhancement remained unclear. In the present study, confluent MDCK renal tubular cell monolayers were scratched to allow cells to proliferate and repair the injured site. At 12-h post-scratch, the repairing cells had significant increases in crystal adhesion capacity and cell proliferation as compared to the control. Cell cycle analysis using flow cytometry demonstrated that the repairing cells underwent cell cycle shift from G0/G1 to S and G2/M phases. Cyclosporin A (CsA) and hydroxyurea (HU) at sub-toxic doses caused cell cycle shift mimicking that observed in the repairing cells. Crystal-cell adhesion assay confirmed the increased crystal adhesion capacity of the CsA-treated and HU-treated cells similar to that of the repairing cells. These findings provide evidence indicating that cell cycle shift from G0/G1 to S and G2/M phases is responsible, at least in part, for the increased adhesion of COM crystals on repairing renal tubular cells at the injured site.
肾小管细胞损伤可增强一水草酸钙（COM）晶体在损伤部位的黏附，从而可能增加结石风险。然而，这种增强作用的潜在机制仍不清楚。在本研究中，将汇合的MDCK肾小管细胞单层刮伤，以使细胞增殖并修复损伤部位。刮伤后12小时，与对照组相比，修复中的细胞晶体黏附能力和细胞增殖显著增加。使用流式细胞术进行的细胞周期分析表明，修复中的细胞经历了从G0/G1期到S期和G2/M期的细胞周期转变。亚毒性剂量的环孢素A（CsA）和羟基脲（HU）导致细胞周期转变，类似于在修复中的细胞中观察到的情况。晶体-细胞黏附试验证实，CsA处理组和HU处理组细胞的晶体黏附能力增加，与修复中的细胞相似。这些发现提供了证据，表明从G0/G1期到S期和G2/M期的细胞周期转变至少部分导致了COM晶体在损伤部位修复中的肾小管细胞上黏附增加。
