Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
Clinical Science, Philips Healthcare, Shanghai 200072, China.
Exp Biol Med (Maywood). 2023 Feb;248(4):327-338. doi: 10.1177/15353702221147569. Epub 2023 Jan 30.
Renal fibrosis is a hallmark of chronic kidney disease, while efficient therapy against renal fibrosis is still lacking. In this study, we investigated the role of a novel small-molecule compound VCP979 on renal fibrosis and inflammation in a rat model of unilateral ureteral obstruction (UUO). One week after the UUO surgery, rats were administered VCP979 by gavage for one week, and after treatment, magnetic resonance imaging of T1rho mapping and histopathological analysis were performed to evaluate renal fibrosis and . This study showed that treatment with VCP979 effectively reduced renal fibrosis, extracellular matrix accumulation, and alleviated epithelial-mesenchymal transition in UUO rats, as well as improved renal function. T1rho mapping displayed increased T1rho values in the UUO rats, which was decreased after VCP979 treatment, and a positive correlation was detected between the T1rho values and the percentage of fibrotic area. Moreover, the administration of VCP979 also ameliorated the inflammatory cytokines expression and the infiltration of macrophages in renal tissues. Mechanistically, VCP979 treatment inhibited the activation of p38 mitogen-activated protein kinase, nuclear factor-kappa B, and transforming growth factor-β1/Smads signaling pathways. These results indicated that VCP979 could be an effective therapeutic agent for alleviating renal fibrosis and inflammation in the rat model of UUO via its antifibrotic and anti-inflammatory effects.
肾纤维化是慢性肾脏病的一个标志，而有效的肾纤维化治疗方法仍然缺乏。在这项研究中，我们研究了一种新型小分子化合物 VCP979 对单侧输尿管梗阻 (UUO) 大鼠模型中肾纤维化和炎症的作用。UUO 手术后 1 周，通过灌胃给予 VCP979 治疗 1 周，治疗后进行 T1rho 映射磁共振成像和组织病理学分析，以评估肾纤维化和炎症。本研究表明，VCP979 治疗有效减少了 UUO 大鼠的肾纤维化、细胞外基质积累和上皮-间充质转化，并改善了肾功能。T1rho 映射显示 UUO 大鼠的 T1rho 值增加，VCP979 治疗后降低，T1rho 值与纤维化面积百分比之间存在正相关。此外，VCP979 的给药还改善了肾脏组织中炎症细胞因子的表达和巨噬细胞的浸润。机制上，VCP979 治疗抑制了 p38 丝裂原活化蛋白激酶、核因子-κB 和转化生长因子-β1/Smads 信号通路的激活。这些结果表明，VCP979 可能通过其抗纤维化和抗炎作用成为 UUO 大鼠模型中缓解肾纤维化和炎症的有效治疗剂。
