Tubulointerstitial fibrosis is the end‐point of chronic kidney diseases. Tamoxifen, a selective oestrogen receptor (ER) modulator, attenuates renal fibrosis, by regulating the transforming growth factor (TGF)‐β/Smad signalling. Src and phosphoinositide 3‐kinase (PI3K)/Akt pathways play critical roles in the pathogenesis of renal fibrosis. However, the activation of the non‐canonical TGF‐β signalling in renal fibrosis after treatment with tamoxifen remains unclear. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in rats. Tamoxifen was orally administered after UUO. Additionally, HK‐2 cells were treated with tamoxifen in the presence or absence of TGF‐β1. The selective ER down‐regulator ICI and ER‐α silencing were used to confirm the involvement of ER‐α on the effect of tamoxifen on TGF‐β1‐stimulated fibrosis in HK‐2 cells.

中文翻译：

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他莫昔芬通过 Src 和 PI3K/Akt/mTOR 通路改善梗阻性肾病

肾小管间质纤维化是慢性肾脏疾病的终点。他莫昔芬是一种选择性雌激素受体 (ER) 调节剂，通过调节转化生长因子 (TGF)-β/Smad 信号传导来减轻肾纤维化。Src 和磷酸肌醇 3-激酶 (PI3K)/Akt 通路在肾纤维化的发病机制中起关键作用。然而，他莫昔芬治疗后肾纤维化中非经典 TGF-β 信号传导的激活仍不清楚。大鼠单侧输尿管梗阻 (UUO) 诱发肾纤维化。在 UUO 后口服他莫昔芬。此外，在存在或不存在 TGF-β1 的情况下，用他莫昔芬处理 HK-2 细胞。使用选择性 ER 下调因子 ICI 和 ER-α 沉默来证实 ER-α 参与他莫昔芬对 HK-2 细胞中 TGF-β1 刺激的纤维化的影响。