Workflow
男性为何容易肾损伤?最新Nature论文证实,雌激素可抵抗铁死亡及其所致的急性肾损伤
生物世界·2025-08-15 04:21

Core Viewpoint - The study published in Nature reveals that estrogen can inhibit ferroptosis and acute kidney injury (AKI), providing insights into the gender differences observed in AKI susceptibility, with men and postmenopausal women being more prone to this condition compared to premenopausal women [2][4][6]. Summary by Sections Gender Differences in AKI - Research indicates that men have a higher incidence and mortality rate from AKI compared to women, particularly when comparing to premenopausal women [4]. - The study suggests that this gender difference may be linked to the sensitivity of acute tubular necrosis (ATN) to ferroptosis, a major type of cell death in AKI [4]. Role of Estrogen - The research focuses on the protective role of estrogen against ferroptosis, demonstrating that estrogen can significantly inhibit cell death mediated by ferroptosis in female renal tubules [4][6]. - Estrogen, specifically 17β-estradiol, establishes an anti-ferroptotic state through both genomic and non-genomic mechanisms, including: - Direct inhibition of ferroptosis by hydroxylated estrogen derivatives, which act as free radical scavengers [4]. - The FSP1-mediated regeneration of oxidized hydroxylated estrogen, indicating a complex interplay in the protective mechanisms [4]. - Regulation by estrogen receptor ESR1, which enhances the anti-ferroptotic capacity of renal tubules [4][6]. Implications for Kidney Protection - The findings elucidate the mechanisms by which female renal tubules resist ferroptosis, explaining the increased susceptibility to AKI in men and postmenopausal women due to decreased estrogen levels [6]. - This research suggests potential therapeutic approaches for kidney protection in males and postmenopausal females, such as the use of estrogen metabolites or ferroptosis inhibitors [6]. - The study emphasizes the importance of gender as a biological variable in the regulation of ferroptosis, with broader implications beyond kidney diseases, potentially affecting conditions like heart disease and stroke [6].