Abstract：
Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.
摘要：
网状蛋白3（RTN3）是一种内质网（ER）蛋白，已被报道在神经退行性疾病和脂质代谢中起作用。然而,尚未研究RTN3在急性肾损伤（AKI）中的作用。这里,我们使用公共数据集，患者数据,和动物模型探讨RTN3在AKI中的作用。在原代肾小管上皮细胞和HK2细胞系中研究了潜在的机制。我们发现在AKI患者中RTN3的表达降低，顺铂诱导的小鼠，和顺铂处理的HK2细胞。在顺铂治疗后,RTN3无效小鼠表现出更严重的AKI症状和肾纤维化。在RTN3敲低或敲除的细胞中也发现了线粒体功能障碍。一项机制研究表明，RTN3可以与肾细胞中的HSPA9相互作用。RTN3缺乏可能会破坏RTN3-HSPA9-VDAC2复合物，并在ER-线粒体接触期间影响MAM，这进一步导致线粒体功能障碍并加剧顺铂诱导的AKI。我们的研究表明，RTN3在肾脏中很重要，肾脏中RTN3的减少可能是AKI加重的危险因素。
