Yan Xu, Zhao Kun, Yao Ye, Wang Lihui, Shan Wei, Zhang Yan
Department of Nephrology, The Second Affiliated Hospital of Qiqihar Medical University, 161006 Qiqihar, Heilongjiang, China.
College of Basic Medical Sciences, Qiqihar Medical University, 161006 Qiqihar, Heilongjiang, China.
Front Biosci (Landmark Ed). 2025 Jul 29;30(7):26076. doi: 10.31083/FBL26076.
Chronic kidney disease (CKD), driven by progressive renal fibrosis, lacks effective therapeutic targets. This study investigates thrombospondin-4 (THBS4) as a novel mediator of CKD-related fibrosis and explores its mechanistic basis.
This study collected 100 patients diagnosed with chronic kidney disease and 30 healthy individuals. Enzyme-linked immunosorbent assay (ELISA) analysis was conducted to assess the expression of THBS4 in CKD patients. Mouse unilateral ureteral obstruction (UUO) renal fibrosis model and Human Kidney-2 (HK2) cell fibrosis model were constructed to analyze the expression changes of THBS4 in renal fibrosis. To examine the effects of inhibiting THBS4 expression on the process of renal fibrosis, these two models were analyzed using Sirius red staining, Masson staining, immunohistochemistry, real-time quantitative PCR (qPCR) and western blot methods.
The expression of THBS4 in the serum of CKD patients was found to be significantly higher ( < 0.05), and its concentration showed a negative correlation with the eGFR levels (r = -0.77, < 0.05) and an increase corresponding to the progression of CKD stages ( < 0.05). THBS4 expression was dramatically increased in UUO-treated mouse kidneys as well as in TGF-β1-stimulated HK2 cells ( < 0.05). , the expression of renal fibrosis-associated proteins was also significantly reduced after interfering with THBS4 expression ( < 0.05). UUO-induced renal fibrosis and related protein expression were suppressed in knockdown mice when compared to control mice ( < 0.05). The levels of p-AKT and p-PI3K exhibited a significant rise in conjunction with the onset of renal fibrosis ( < 0.05). The expression of p-AKT as well as p-PI3K showed a significant reduction upon inhibition of THBS4 expression ( < 0.05). Insulin-like growth factor 1 (IGF-1) treatment reversed these effects.
THBS4 was significantly overexpressed in CKD patients. By suppressing the expression of proteins associated with renal fibrosis and inhibiting the activation of the PI3K/AKT pathway, THBS4 has the potential to mitigate renal fibrosis.
慢性肾脏病（CKD）由进行性肾纤维化驱动，缺乏有效的治疗靶点。本研究调查血小板反应蛋白-4（THBS4）作为CKD相关纤维化的一种新型介质，并探讨其作用机制。
本研究收集了100例诊断为慢性肾脏病的患者和30名健康个体。采用酶联免疫吸附测定（ELISA）分析评估CKD患者中THBS4的表达。构建小鼠单侧输尿管梗阻（UUO）肾纤维化模型和人肾2（HK2）细胞纤维化模型，分析肾纤维化中THBS4的表达变化。为了研究抑制THBS4表达对肾纤维化进程的影响，使用天狼星红染色、Masson染色、免疫组织化学、实时定量PCR（qPCR）和蛋白质印迹法对这两种模型进行分析。
发现CKD患者血清中THBS4的表达显著升高（<0.05），其浓度与估算肾小球滤过率（eGFR）水平呈负相关（r=-0.77，<0.05），并随CKD分期进展而升高（<0.
