丹参酮 I 通过下调抑制素β -A减轻肾纤维化。
Tanshinone I attenuates fibrosis in fibrotic kidneys through down-regulation of inhibin beta-A.
作者信息
Wu Ming, Yang Feng, Huang Di, Ye Chaoyang
机构信息
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528 Zhangheng Road, Pudong District, Shanghai, 201203, PR China.
TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
BMC Complement Med Ther. 2022 Apr 19;22(1):110. doi: 10.1186/s12906-022-03592-3.
BACKGROUND
Tanshinone I (Tan-I), an ingredient of Salvia miltiorrhiza, displays protective effects in several disease models. We aim to study the effect of Tan-I on renal fibrosis and explore its underlining mechanism.
METHODS
Rat renal fibroblasts (NRK-49F) were used as an in vitro model to study the effect of Tan-I. Mouse renal fibrosis model was induced by unilateral ureteral obstruction (UUO) or peritoneally injection of aristolochic acid I (AAI).
RESULTS
We found that Tan-I dose-dependently inhibited the expression of pro-fibrotic markers in rat renal fibroblasts. Masson staining and Western blotting analysis showed that Tan-I treatment attenuated renal fibrosis in UUO or AAI induced fibrotic kidneys. RNA sequencing analysis identified inhibin beta-A (INHBA), a ligand of TGF-β superfamily, as a downstream target of Tan-I in fibrotic kidneys, which were further verified by qPCR. Western blotting analysis showed that INHBA is up-regulated in UUO or AAI induced fibrotic kidneys and Tan-I reduced the expression of INHBA in fibrotic kidneys. Inhibition of INHBA by Tan-I was further confirmed in rat fibroblasts. Moreover, knockdown of INHBA reduced the expression of pro-fibrotic markers and abolished the ani-fibrotic effect of Tan-I in rat renal fibroblasts.
CONCLUSIONS
We conclude that Tan-I attenuates fibrosis in fibrotic kidneys through inhibition of INHBA.
背景
丹参酮 I（Tan-I）是丹参的一种成分，在多种疾病模型中显示出保护作用。我们旨在研究 Tan-I 对肾纤维化的影响并探索其潜在机制。
方法
使用大鼠肾成纤维细胞（NRK-49F）作为体外模型来研究 Tan-I 的作用。通过单侧输尿管梗阻（UUO）或腹腔注射马兜铃酸 I（AAI）诱导小鼠肾纤维化模型。
结果
我们发现 Tan-I 剂量依赖性地抑制大鼠肾成纤维细胞中促纤维化标志物的表达。Masson 染色和蛋白质印迹分析表明，Tan-I 处理减轻了 UUO 或 AAI 诱导的纤维化肾脏中的肾纤维化。RNA 测序分析确定抑制素β-A（INHBA），一种 TGF-β超家族的配体，作为 Tan-I 在纤维化肾脏中的下游靶点，这通过 qPCR 进一步验证。蛋白质印迹分析表明，INHBA 在 UUO 或 AAI 诱导的纤维化肾脏中上调，而 Tan-I 降低了纤维化肾脏中 INHBA 的表达。Tan-I 对 INHBA 的抑制作用在大鼠成纤维细胞中得到进一步证实。此外，敲低 INHBA 降低了促纤维化标志物的表达，并消除了 Tan-I 在大鼠肾成纤维细胞中的抗纤维化作用。
结论
我们得出结论，Tan-I 通过抑制 INHBA 减轻纤维化肾脏中的纤维化。
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