인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Neutrophil elastase (Elane) is upregulated in metabolic-associated fatty liver disease (MAFLD) and has the capacity to promote disease progression. However, the mechanism by which Elane promotes MAFLD development remains unclear. Ferroptosis, which is an iron-dependent nonapoptotic form of cell death characterized by the iron-induced accumulation of lipid reactive oxygen species (ROS), has been recently considered as an important mechanism for the development of MAFLD. In this study, we used mice of Elane-knockout (Elane-KO) and wild-type (WT), and their primary mouse hepatocytes to establish MAFLD models in vivo and vitro for elucidating the role of Elane in ferroptosis of hepatocytes and MAFLD development. Elane-KO in vivo reduced high-fat diet (HFD) induced hepatic lipid peroxidation levels and the proportion of hepatocyte death, upregulated the expression of Nrf2 and Gpx4, and downregulated Keap1 expression. Treatment with recombinant Elane increased the lipid peroxidation level of hepatocytes, increased the ferroptosis rate of hepatocytes, upregulated the expression of Keap1, enhanced the ubiquitination of Nrf2, and downregulated the expression of Nrf2 and Gpx4 in an FFA-induced MAFLD in vitro model. However, primary hepatocytes from Elane-KO mice presented opposite changes. Furthermore, an in vitro experiment revealed that Elane enhanced the protein stability of Keap1 and thus increased Keap1 expression in hepatocytes by inhibiting the lysosomal degradation of the Keap1 protein. Finally, in vitro Co-IP experiments revealed that Elane increased the protein stability of Keap1 by weakening the binding between P62 and Keap1 and ultimately promoted hepatocyte Nrf2 ubiquitination and ferroptosis in MAFLD. In conclusion, our results suggested that Elane promoted hepatocyte ferroptosis in MAFLD through the P62-Keap1-Nrf2-Gpx4 axis. Elane promotes ferroptosis in hepatocytes from fatty livers. Elane reduces the binding of P62 to Keap1, thereby increasing Keap1 protein stability and subsequently inhibiting the Nrf2/Gpx4 pathway, ultimately leading to ferroptosis in hepatocytes.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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