Life Sciences ( IF 5.2 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.lfs.2021.119946 Jing Pan 1 , Min Shi 2 , Fan Guo 2 , Liang Ma 2 , Ping Fu 2
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Aims
Kidney fibrosis is a histological hallmark of chronic kidney disease (CKD), where hyperuricemia is a key independent risk factor. Considerable evidence indicated that STAT3 is one of the crucial signaling pathways in the progression of kidney fibrosis. Here, we investigated that pharmacological blockade of STAT3 delayed the progression of renal fibrosis in hyperuricemia-induced CKD.
Main methods
In the study, we used the mixture of adenine and potassium oxonate to perform kidney injury and fibrosis in hyperuricemic mice, accompanied by STAT3 activation in tubular and interstitial cells.
Key findings
Treatment with STAT3 inhibitor S3I-201 improved renal dysfunction, reduced serum uric acid level, and delayed the progression of kidney fibrosis. Furthermore, S3I-201 could suppress fibrotic signaling pathway of TGF-β/Smads, JAK/STAT and NF-κB, as well as inhibit the expression of multiple profibrogenic cytokines/chemokines in the kidneys of hyperuricemic mice.
Significance
These data suggested that STAT3 inhibition was a potent anti-fibrotic strategy in hyperuricemia-related CKD.
中文翻译：
药理学抑制 STAT3 延缓高尿酸血症引起的慢性肾病肾纤维化的进展
宗旨
肾纤维化是慢性肾病 (CKD) 的组织学标志，其中高尿酸血症是关键的独立危险因素。大量证据表明，STAT3 是肾纤维化进展中的关键信号通路之一。在这里，我们研究了 STAT3 的药理学阻断延迟了高尿酸血症诱导的 CKD 中肾纤维化的进展。
主要方法
在研究中，我们使用腺嘌呤和氧酸钾的混合物对高尿酸血症小鼠进行肾损伤和纤维化，同时在肾小管和间质细胞中激活 STAT3。
主要发现
STAT3 抑制剂 S3I-201 治疗可改善肾功能障碍、降低血清尿酸水平并延缓肾纤维化的进展。此外，S3I-201 可以抑制 TGF-β/Smads、JAK/STAT 和 NF-κB 的纤维化信号通路，并抑制高尿酸血症小鼠肾脏中多种促纤维化细胞因子/趋化因子的表达。
意义
这些数据表明 STAT3 抑制是高尿酸血症相关 CKD 的有效抗纤维化策略。
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