Hiroki Miyano, Amane Endo, Akira Mizutani, Mayu Nakagawa, Koji Sakuraya, Yayoi Murano, Naoto Nishizaki, Shuichiro Fujinaga, Yoshiyuki Ohtomo, Toshiaki Shimizu
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引用次数: 0
Abstract
Background: Reactive oxygen species aggravate renal fibrosis, prompting the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key mediator in the cellular response to oxygen stress. Nrf2 exerts renoprotective effects by upregulating antioxidant response element (ARE)-dependent genes that antagonize renal fibrosis. Elucidating mechanisms to attenuate renal fibrosis in children is essential for developing therapeutic interventions. This study aimed to examine the renoprotective effects of Nrf2 activators on ARE action in rats with unilateral ureteral obstruction (UUO)-induced renal injury.
Methods: The time course of Nrf2 was evaluated in 8-week-old male Sprague-Dawley rats with UUO, with or without Nrf2 activators (bardoxolone methyl) for 2 weeks postoperatively. Kidney tissues were collected on Days 7 and 14 post-surgery. Renoprotective effects were examined using real-time polymerase chain reaction (RT-PCR) and histopathological analyses of kidney samples.
Results: Nrf2 activators reduced the interstitial fibrotic area in UUO kidneys, causing a substantial decline in ED-1-positive cell infiltration and transforming growth factor-β expression. RT-PCR revealed that Nrf2 activators suppressed the expression of renal fibrotic factors and promoted the expression of ARE-dependent genes. Moreover, immunostaining for Nrf2 demonstrated increased nuclear translocation and activation induced by Nrf2 activators.
Conclusions: Nrf2 activators induced nuclear translocation and activation of Nrf2, resulting in upregulation of ARE-dependent genes. Although the function of Nrf2 in children is often unknown, this study may lead to future progress in oxidation and antioxidant function in children.
期刊介绍：
Publishing articles of scientific excellence in pediatrics and child health delivery, Pediatrics International aims to encourage those involved in the research, practice and delivery of child health to share their experiences, ideas and achievements. Formerly Acta Paediatrica Japonica, the change in name in 1999 to Pediatrics International, reflects the Journal''s international status both in readership and contributions (approximately 45% of articles published are from non-Japanese authors). The Editors continue their strong commitment to the sharing of scientific information for the benefit of children everywhere.
Pediatrics International opens the door to all authors throughout the world. Manuscripts are judged by two experts solely upon the basis of their contribution of original data, original ideas and their presentation.
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