Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.
Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hoguk-ro, Bukgu, Daegu 41404, Republic of Korea.
Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1817-1828. doi: 10.1016/j.bbadis.2017.05.004. Epub 2017 May 8.
Acute kidney injury (AKI) is a major complication of hepatic surgeries. The primary cilium protrudes to the lumen of kidney tubules and plays an important role in renal functions. Disruption of primary cilia homeostasis is highly associated with human diseases including AKI. Here, we investigated whether transient hepatic ischemia induces length change and deciliation of kidney primary cilia, and if so, whether reactive oxygen species (ROS)/oxidative stress regulates those. HIR induced damages to the liver and kidney with increases in ROS/oxidative stress. HIR shortened the cilia of kidney epithelial cells and caused them to shed into the urine. This shortening and shedding of cilia was prevented by Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, an antioxidant). The urine of patient undergone liver resection contained ciliary proteins. These findings indicate that HIR induces shortening and deciliation of kidney primary cilia into the urine via ROS/oxidative stress, suggesting that primary cilia is associated with HIR-induced AKI and that the presence of ciliary proteins in the urine could be a potential indication of kidney injury.
急性肾损伤（AKI）是肝手术的主要并发症。初级纤毛向肾小管腔突出，在肾脏功能中发挥重要作用。初级纤毛内稳态的破坏与人的疾病高度相关，包括 AKI。在这里，我们研究了短暂的肝缺血是否会引起肾脏初级纤毛的长度变化和脱纤毛，如果是这样，活性氧（ROS）/氧化应激是否会调节纤毛。HIR 导致肝脏和肾脏损伤，ROS/氧化应激增加。HIR 缩短了肾脏上皮细胞的纤毛，并使其脱落到尿液中。Mn(III)四（1-甲基-4-吡啶基）卟啉（MnTMPyP，一种抗氧化剂）可预防纤毛的缩短和脱落。接受肝切除术的患者的尿液中含有纤毛蛋白。这些发现表明，HIR 通过 ROS/氧化应激诱导肾脏初级纤毛缩短并脱落到尿液中，提示初级纤毛与 HIR 诱导的 AKI 有关，尿液中存在纤毛蛋白可能是肾脏损伤的潜在指标。
