Liu Xiaoming, Wang Huijuan, Wang Kai, Liu Ying
Department of Nephrology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, P.R. China.
Department of Pathology, Yantaishan Hospital, Yantai, Shandong, P.R. China.
PLoS One. 2025 Jul 7;20(7):e0322639. doi: 10.1371/journal.pone.0322639. eCollection 2025.
Chronic kidney disease (CKD) is a global health issue that significantly threatens human health, with its incidence increasing annually. Renal fibrosis is characterized by the progressive loss of kidney function, leading to significant morbidity and mortality. Although ribosome biogenesis has been reported to be increased in several kidney diseases, its role in renal fibrosis remains unclear. This study investigates the role of the interferon-stimulated gene of 20 kDa protein (Isg20), an RNA exonuclease involved in several stages of ribosome biogenesis, in the progression of renal fibrosis. Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets identified upregulation of ribosome biogenesis-related genes and Isg20 expression in renal fibrosis samples. Using the unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model, we confirmed elevated Isg20 expression, promoted renal fibrosis, and increased ribosome biogenesis. Knockdown of Isg20 significantly reduced ribosome biogenesis, ameliorated kidney damage, inhibited pro-inflammatory cytokines levels and renal fibrotic changes, and decreased endoplasmic reticulum stress and cell apoptosis. Our findings suggest that Isg20 exacerbates renal fibrosis by promoting ribosome biogenesis, ER stress and cell apoptosis highlighting a potential therapeutic target for renal fibrosis treatment.
慢性肾脏病（CKD）是一个严重威胁人类健康的全球性卫生问题，其发病率逐年上升。肾纤维化的特征是肾功能进行性丧失，导致高发病率和死亡率。虽然已有报道称核糖体生物发生在几种肾脏疾病中增加，但其在肾纤维化中的作用仍不清楚。本研究调查了参与核糖体生物发生多个阶段的RNA核酸外切酶——20 kDa干扰素刺激基因（Isg20）在肾纤维化进展中的作用。对基因表达综合数据库（GEO）数据集的生物信息学分析确定了肾纤维化样本中核糖体生物发生相关基因和Isg20表达上调。使用单侧输尿管梗阻（UUO）诱导的肾纤维化小鼠模型，我们证实了Isg20表达升高、促进了肾纤维化并增加了核糖体生物发生。敲低Isg20可显著降低核糖体生物发生，改善肾脏损伤，抑制促炎细胞因子水平和肾纤维化变化，并降低内质网应激和细胞凋亡。我们的研究结果表明，Isg20通过促进核糖体生物发生、内质网应激和细胞凋亡加重肾纤维化，这突出了肾纤维化治疗的一个潜在靶点。
