Saracatinib通过抑制Wnt/β-Catenin通路延缓肾间质纤维化进展

IF 3 Q1 UROLOGY & NEPHROLOGY
Kidney360 Pub Date : 2025-09-22 DOI:10.34067/KID.0000000972
Junjun Ma, Nan Jiao, Xingwei Liu, Xiao Lu
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引用次数: 0

摘要

背景:肾间质纤维化是CKD的常见病理特征,是疾病进展的关键决定因素。最近的研究强调了Wnt/β-catenin信号通路在肾间质纤维化发展中的重要作用,但其确切机制尚不清楚。方法:选择2022年1月至2023年12月在本中心接受肾活检的CKD合并肾间质纤维化患者的肾组织样本进行染色。采用单侧输尿管梗阻(UUO)建立大鼠肾间质纤维化模型。给UUO大鼠灌胃低剂量和高剂量萨拉卡替尼2周,观察相关指标变化。结果:在本研究中,我们发现在CKD患者和肾间质纤维化大鼠的肾脏组织中,酪氨酸142激酶Fyn明显上调,并伴有Wnt/β-catenin通路的过度激活。研究发现Saracatinib通过与肾组织中的Fyn结合,从而阻断β-catenin酪氨酸142位点的磷酸化,从而抑制这一途径。该抑制作用1)降低血清尿素氮和胱抑素C水平,升高血清白蛋白和总蛋白浓度;2)减轻单侧输尿管梗阻模型大鼠肾间质纤维化,改善肾间质纤维化的进展。结论:本研究提示saracatinib可能是CKD治疗的一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Saracatinib Delays the Progression of Renal Interstitial Fibrosis by Inhibiting the Wnt/β-Catenin Pathway.

Background: Renal interstitial fibrosis is a common pathological feature of CKD and is a critical determinant of disease progression. Recent studies have highlighted the significant role of the Wnt/β-catenin signaling pathway in the development of renal interstitial fibrosis, but the exact mechanisms remain unclear.

Methods: Renal tissue samples from CKD patients with renal interstitial fibrosis who underwent renal biopsy at our center between January 2022 and December 2023 were selected for staining. Additionally, a rat model of renal interstitial fibrosis was established using unilateral ureteral obstruction (UUO). UUO rats were administered low- and high-dose doses of saracatinib via gavage for two weeks, followed by examination of changes in relevant indicators.

Results: In this study, we showed that in the kidney tissues of both CKD patients and rats with renal interstitial fibrosis, there was a marked upregulation of the tyrosine 142 kinase Fyn, which accompanied the excessive activation of the Wnt/β-catenin pathway. Saracatinib was found to inhibit this pathway by binding to Fyn in kidney tissues, thereby blocking the phosphorylation of β-catenin at tyrosine 142. This inhibition 1) decreased the serum urea nitrogen and cystatin C levels, along with an increase in serum albumin and total protein concentration, 2) alleviated renal interstitial fibrosis in the unilateral ureteral obstruction rat model, resulting in an amelioration of the progression of renal interstitial fibrosis.

Conclusions: This study suggests that saracatinib may be a novel therapeutic strategy for CKD treatment.

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来源期刊
Kidney360
Kidney360 UROLOGY & NEPHROLOGY-
CiteScore
3.90
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