The Journal of surgical research · 2026
Redox Imbalance and Impaired Protein Clearance Drive Chronic Liver Injury in Biliary Atresia.
СтатьяНазвание и аннотация: Перевод в очереди
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Nakagawa Yoichi, Kitajima Satoshi, Tainaka Takahisa, Shirota Chiyoe, Makita Satoshi, Yasui Akihiro, Kato Daiki, Ishii Hiroki, Liu Jiahui, Uchida Hiroo
Аннотация
INTRODUCTION: Excessive or uncontrolled generation of reactive oxygen species (ROS) is closely associated with the development of liver diseases. However, direct evidence linking oxidative stress to impaired hepatic function in human biliary atresia (BA) remains limited. To address this, we performed bulk RNA sequencing to investigate (1) alterations in hepatic oxidative stress and antioxidant defense mechanisms and (2) transcriptomic changes associated with impaired hepatic function in BA.
METHODS: Total RNA was extracted from liver samples of patients with BA and non-BA cholestasis. Bulk RNA sequencing and transcriptomic analyses were performed, focusing on redox-related pathways and genes linked to hepatic function.
RESULTS: Dual oxidases 1 and 2 were significantly upregulated in BA. In contrast, key ROS-metabolizing enzymes such as catalase, glutathione synthetase, and superoxide dismutase 1 and 2 were downregulated, indicating redox imbalance in BA livers. Excessive ROS can lead to the denaturation of cellular proteins and damage to organelles, which are normally degraded via autophagy and proteasomes. However, both autophagy and proteasome functions were impaired in BA, contributing to sustained inflammation and further ROS production. Transcriptomic analyses also revealed repression of core liver transcription and splicing factors, indicating injury-associated alterations in hepatic transcription programs.
CONCLUSIONS: BA is characterized by a redox imbalance and dysfunctional protein clearance, forming a vicious cycle of ROS accumulation and inflammation. These changes likely contribute to liver fibrosis and the progressive loss of hepatic function in BA.
METHODS: Total RNA was extracted from liver samples of patients with BA and non-BA cholestasis. Bulk RNA sequencing and transcriptomic analyses were performed, focusing on redox-related pathways and genes linked to hepatic function.
RESULTS: Dual oxidases 1 and 2 were significantly upregulated in BA. In contrast, key ROS-metabolizing enzymes such as catalase, glutathione synthetase, and superoxide dismutase 1 and 2 were downregulated, indicating redox imbalance in BA livers. Excessive ROS can lead to the denaturation of cellular proteins and damage to organelles, which are normally degraded via autophagy and proteasomes. However, both autophagy and proteasome functions were impaired in BA, contributing to sustained inflammation and further ROS production. Transcriptomic analyses also revealed repression of core liver transcription and splicing factors, indicating injury-associated alterations in hepatic transcription programs.
CONCLUSIONS: BA is characterized by a redox imbalance and dysfunctional protein clearance, forming a vicious cycle of ROS accumulation and inflammation. These changes likely contribute to liver fibrosis and the progressive loss of hepatic function in BA.