Yu Bang-Xian, Long Jun, Liang Ye-Ping, Zhang Quan, Liu Yang, Zeng Guo-Hua, Liu Yong-Da, Sun Xin-Yuan
Guangdong Provincial Key Laboratory of Urological Diseases, Department of Urology, Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Commun Biol. 2025 Sep 2;8(1):1330. doi: 10.1038/s42003-025-08757-7.
Calcium salt deposition in the kidney induces epithelial-to-mesenchymal transition (EMT) in renal tubular epithelial cells, which is the pathological basis for the progression to renal fibrosis in patients with renal stones; however, effective drugs to prevent and treat this disease have not been adequately investigated. In this study, we conducted a comprehensive analysis of fibrosis-related core genes by utilizing bioinformatics on RNA-seq data, along with web database information. Additionally, we designed both in vivo and in vitro experiments to elucidate the mechanisms and signaling pathways through which Desmodium styracifolium polysaccharides (Ds) mitigate renal fibrosis induced by nephrolithiasis. Renal fibrosis is present in both patients afflicted with calcium oxalate (CaOx) stones and in model rats. RNA-seq analysis and network database examination identified TGF-β as a fibrosis-related core gene. Moreover, Ds were found to accumulate in the kidneys of these model rats, effectively reducing crystalline deposits, mitigating renal injury, and alleviating renal fibrosis. Ds effectively attenuated nano-CaOx-induced HK-2 damage and delayed the EMT process by interfering with TGF-β expression and secretion and inhibiting the activation of the TGF-β/Smad pathway in vitro. Ds may emerge as a potential therapeutic option for the clinical treatment of crystalline renal fibrosis.
肾脏中的钙盐沉积会诱导肾小管上皮细胞发生上皮-间质转化（EMT），这是肾结石患者进展为肾纤维化的病理基础；然而，预防和治疗这种疾病的有效药物尚未得到充分研究。在本研究中，我们利用生物信息学对RNA测序数据以及网络数据库信息进行了纤维化相关核心基因的综合分析。此外，我们设计了体内和体外实验，以阐明广金钱草多糖（Ds）减轻肾结石诱导的肾纤维化的机制和信号通路。草酸钙（CaOx）结石患者和模型大鼠均存在肾纤维化。RNA测序分析和网络数据库检查确定TGF-β为纤维化相关核心基因。此外，发现Ds在这些模型大鼠的肾脏中蓄积，有效减少晶体沉积，减轻肾损伤，并缓解肾纤维化。在体外，Ds通过干扰TGF-β的表达和分泌并抑制TGF-β/Smad通路的激活，有效减轻纳米CaOx诱导的HK-2损伤并延缓EMT进程。Ds可能成为临床治疗晶体性肾纤维化的一种潜在治疗选择。
