Etoposide‐induced 2.4 (EI24) exerts tumor suppressor activity through participating in cell apoptosis, autophagy, and inflammation. However, its role in renal diseases has not been elucidated. This study showed that the EI24 level decreased gradually in the kidneys of mice with unilateral ureteral obstruction (UUO) and in another fibrosis model induced by diabetic kidney disease. The overexpression of EI24 was used to investigate the possible role both in vivo and in vitro. The overexpression 1 day after UUO through tail vein injection alleviated the progression of renal interstitial fibrosis (RIF). EI24 inhibited epithelial‐mesenchymal transition, excessive deposition of the extracellular matrix, and activation of fibroblasts. Furthermore, administration of EI24‐overexpressing plasmids restrained the phosphorylation of nuclear factor‐κB (NF‐κB) and c‐Jun kinase (JNK) through regulating the proteasome‐dependent degradation of TRAF2, and then, inhibited the expression of downstream inflammation‐associated cytokines (interleukin‐6, tumor necrosis factor‐α, and monocyte chemotactic protein‐1) and infiltration of macrophages and neutrophils in mouse kidney after UUO. In conclusion, the data indicated that EI24, a novel anti‐fibrosis regulator, was important in the progression of RIF.

中文翻译：

---

EI24通过抑制上皮间质转化和成纤维细胞活化减轻肾间质纤维化

依托泊苷诱导的 2.4 (EI24) 通过参与细胞凋亡、自噬和炎症发挥肿瘤抑制活性。然而，其在肾脏疾病中的作用尚未阐明。本研究表明，单侧输尿管梗阻 (UUO) 小鼠肾脏和另一种糖尿病肾病诱导的纤维化模型中 EI24 水平逐渐降低。EI24 的过表达用于研究体内和体外的可能作用。通过尾静脉注射 UUO 后 1 天的过表达减轻了肾间质纤维化 (RIF) 的进展。EI24 抑制上皮间质转化、细胞外基质的过度沉积和成纤维细胞的活化。此外，EI24过表达质粒的给药通过调节TRAF2的蛋白酶体依赖性降解来抑制核因子-κB（NF-κB）和c-Jun激酶（JNK）的磷酸化，然后抑制下游炎症相关细胞因子的表达。白细胞介素-6、肿瘤坏死因子-α和单核细胞趋化蛋白-1)以及UUO后小鼠肾脏中巨噬细胞和中性粒细胞的浸润。总之，数据表明 EI24，一种新型的抗纤维化调节剂，在 RIF 的进展中很重要。和单核细胞趋化蛋白-1）以及 UUO 后小鼠肾脏中巨噬细胞和中性粒细胞的浸润。总之，数据表明 EI24，一种新型的抗纤维化调节剂，在 RIF 的进展中很重要。和单核细胞趋化蛋白-1）以及 UUO 后小鼠肾脏中巨噬细胞和中性粒细胞的浸润。总之，数据表明 EI24，一种新型的抗纤维化调节剂，在 RIF 的进展中很重要。