FoxM1 is a transcriptional regulator involved in tumor development, pulmonary fibrosis, and cardiac fibrosis. However, its role in renal interstitial fibrosis (RIF) has yet to be elucidated. We established a TGF-β1-stimulated human proximal tubular epithelial cell (HK-2) model in vitro and a unilateral ureteral obstruction (UUO)-induced rat RIF model in vivo. FoxM1 inhibition was achieved by siRNA interference in vitro and by injecting thiostrepton into UUO-induced RIF rats in vivo. The degree of renal damage and fibrosis were determined by histological assessment via hematoxylin and eosin (H&E) staining. Immunohistochemistry, western blots, and qPCR were used to determine the expression levels of FoxM1, Collagen I, E-cadherin, α-SMA, and Snail1. Our results showed that FoxM1 inhibition could ameliorate RIF and reduce the deposition of Collagen I. H&E staining revealed that renal structural damage, inflammatory cell infiltration, and ECM deposition were significantly attenuated by thiostrepton treatment in the UUO rats. Furthermore, FoxM1 downregulation significantly suppressed epithelial-to-mesenchymal transition, as evidenced by decreased protein and mRNA expression levels of α-SMA and Snail1 and a significant increase in protein and mRNA expression levels of E-cadherin. Collectively, these results suggested that FoxM1 inhibition could be a novel therapeutic strategy for the treatment of RIF.

FoxM1是涉及肿瘤发展，肺纤维化和心脏纤维化的转录调节因子。然而，其在肾间质纤维化（RIF）中的作用尚待阐明。我们建立了TGF-β1刺激的人近端肾小管上皮细胞（HK-2）模型在体外和单侧输尿管梗阻（UUO）诱导的大鼠模型RIF体内。FoxM1抑制是通过体外siRNA干扰和通过将硫链丝菌素注射到UUO诱导的RIF大鼠体内来实现的。肾损伤和纤维化程度通过苏木精和曙红（H＆E）染色的组织学评估确定。免疫组化，免疫印迹和qPCR用于确定FoxM1，胶原I，E-钙黏着蛋白，α-SMA和Snail1的表达水平。我们的研究结果表明，FoxM1抑制作用可以改善RIF并减少胶原I的沉积。H＆E染色显示，硫脲类链球菌素治疗可明显减轻UUO大鼠的肾脏结构损伤，炎症细胞浸润和ECM沉积。此外，FoxM1的下调显着抑制了上皮到间充质的转化，这可以通过α-SMA和Snail1的蛋白质和mRNA表达水平降低以及E-钙黏着蛋白的蛋白质和mRNA表达水平显着增加来证明。总的来说，