Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Biomed Res Int. 2020 Dec 10;2020:9029868. doi: 10.1155/2020/9029868. eCollection 2020.
Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.
内质网应激（ERS）与急性肾损伤（AKI）向慢性肾脏病（CKD）的转变密切相关。槐耳提取物（HE）可预防肾损伤；然而，其潜在机制尚不清楚。我们假设 HE 通过抑制 ERS 来减轻肾损伤。在这项研究中，我们使用缺血再灌注损伤（IRI）的 AKI-CKD 小鼠模型，评估了 HE 对 AKI-CKD 转变的影响。我们还在该动物模型和 HK-2 人肾细胞系中探索了潜在的分子机制。结果表明，HE 治疗可改善肾功能，IRI 后血清肌酐水平显著降低证明了这一点。HE 可明显减轻肾损伤和纤维化程度，并在 IRI 后恢复 miR-1271 的表达。此外，HE 可降低 ERS 标志物葡萄糖调节蛋白 78（GRP78）和 C/EBP 同源蛋白（CHOP）的表达，并抑制 IRI 组的细胞凋亡。HE 抑制 ERS 诱导的细胞凋亡和降低 CHOP 和 GRP78 的表达的体外结果支持了这一体内作用。我们证明 CHOP 是 miR-1271 的靶标。总之，HE 通过上调 miR-1271 抑制细胞凋亡和降低 GRP78 和 CHOP 的表达来减轻肾损伤。
