Caffeine has been demonstrated to possess anti-fibrotic activity against liver fibrosis. However, its role in renal fibrosis remained unclear. This study investigated the effects of caffeine on renal fibroblast activation induced by hypoxia (one of the inducers for renal fibrosis). BHK-21 fibroblasts were cultured under normoxia or hypoxia with or without caffeine treatment. Hypoxia increased levels of fibronectin, α-smooth muscle actin, actin stress fibers, intracellular reactive oxygen species (ROS), and oxidized proteins. However, caffeine successfully preserved all these activated fibroblast markers to their basal levels. Cellular catalase activity was dropped under hypoxic condition but could be reactivated by caffeine. Hif1a gene and stress-responsive Nrf2 signaling molecule were elevated/activated by hypoxia, but only Nrf2 could be partially recovered by caffeine. These data suggest that caffeine exhibits anti-fibrotic effect against hypoxia-induced renal fibroblast activation through its antioxidant property to eliminate intracellular ROS, at least in part, via downstream catalase and Nrf2 mechanisms.

中文翻译：

---

咖啡因通过抗氧化剂机制抑制缺氧诱导的肾成纤维细胞活化。

咖啡因已被证明具有抗肝纤维化的抗纤维化活性。然而，其在肾纤维化中的作用仍不清楚。这项研究调查了咖啡因对缺氧（肾纤维化的诱因之一）诱导的肾成纤维细胞活化的影响。在有氧或无咖啡因处理的常氧或低氧条件下培养BHK-21成纤维细胞。缺氧会增加纤连蛋白，α平滑肌肌动蛋白，肌动蛋白应激纤维，细胞内活性氧（ROS）和氧化蛋白的水平。然而，咖啡因成功地将所有这些活化的成纤维细胞标记物保持在其基础水平。低氧条件下细胞的过氧化氢酶活性下降，但可以被咖啡因激活。Hif1a基因和​​应激反应性Nrf2信号分子被缺氧升高/激活，但是咖啡因只能部分回收Nrf2。这些数据表明，咖啡因通过其抗氧化特性至少部分地通过下游过氧化氢酶和Nrf2机理消除细胞内ROS，具有抗缺氧诱导的肾成纤维细胞活化的抗纤维化作用。