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Background <p>Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.</p> Methods <p>We constructed the rat model of sham, UUO, UUO + low (10 IU/kg), medium (20 IU/kg) and high (40 IU/kg) doses of KAR groups in vivo, and we analyzed pathologic changes and expression of vimentin and α-smooth muscle actin (α-SMA), cluster of differentiation group 206, F4/80, FN, Snail1, Kim1, small mother against decapentaplegic (Smad) 3 and transforming growth factor-beta [TGF-β1]. Furthermore, we developed the HK-2 cell fibrosis model using TGF-β1 (5 ng/ml) for 24&#xa0;h in vitro. We used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry to detect α-SMA protein, TGF-β1, Smad3, and p-Smad3 levels in renal tissues. We examine protein levels of the Keap1/Nrf2 pathway using the Nrf-2 inhibitor, ML385, and downregulation of Nrf-2 expression using Western blotting.</p> Results <p>Our results revealed that KAR improved renal function and downregulated α-SMA protein. Furthermore, KAR induced the polarization of M2 macrophages. KAR improved fibrosis by inhibiting the TGF-β1/Smad3 pathway. KAR inhibited renal fibrosis and inflammation by activating the Keap1/Nrf2 pathway in vivo and in vitro.</p> Conclusions <p>KAR inhibited renal fibrosis and inflammation through the Keap1/Nrf-2 pathway, indicating that it may become a small molecular drug for chronic kidney disease.</p>

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Kurarinone protects against renal injury and fibrosis after unilateral ureteral obstruction through enhancement of the Nrf-2 signaling pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月29日

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  • Tiancao Dong,
  • Dongyang Zhao,
  • Sen Jiang,
  • Yi Gu,
  • Chunxue Wang,
  • Qian Yang,
  • Tong Liu,
  • Xiandong Liu

摘要

Background

Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.

Methods

We constructed the rat model of sham, UUO, UUO + low (10 IU/kg), medium (20 IU/kg) and high (40 IU/kg) doses of KAR groups in vivo, and we analyzed pathologic changes and expression of vimentin and α-smooth muscle actin (α-SMA), cluster of differentiation group 206, F4/80, FN, Snail1, Kim1, small mother against decapentaplegic (Smad) 3 and transforming growth factor-beta [TGF-β1]. Furthermore, we developed the HK-2 cell fibrosis model using TGF-β1 (5 ng/ml) for 24 h in vitro. We used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry to detect α-SMA protein, TGF-β1, Smad3, and p-Smad3 levels in renal tissues. We examine protein levels of the Keap1/Nrf2 pathway using the Nrf-2 inhibitor, ML385, and downregulation of Nrf-2 expression using Western blotting.

Results

Our results revealed that KAR improved renal function and downregulated α-SMA protein. Furthermore, KAR induced the polarization of M2 macrophages. KAR improved fibrosis by inhibiting the TGF-β1/Smad3 pathway. KAR inhibited renal fibrosis and inflammation by activating the Keap1/Nrf2 pathway in vivo and in vitro.

Conclusions

KAR inhibited renal fibrosis and inflammation through the Keap1/Nrf-2 pathway, indicating that it may become a small molecular drug for chronic kidney disease.