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
The ubiquitin-editing enzyme A20 is known to regulate inflammation and maintain homeostasis, but its role in self-DNA-mediated inflammation in acute kidney injury (AKI) is not well understood. Here, our study demonstrated that oxidized self-DNA accumulates in the serum of AKI mice and patients. This oxidized self-DNA exacerbates the progression of AKI by activating the cGAS-STING pathway and NLRP3 inflammasome. While inhibition of the STING pathway only slightly attenuates AKI progression, suppression of NLRP3 inflammasome-mediated pyroptosis significantly alleviates AKI progression and improves the survival of AKI mice. Subsequently, we found that Tnfaip3 (encoding A20) is significantly upregulated following oxidized self-DNA treatment. A20 significantly alleviates AKI development by dampening STING signaling pathway and NLRP3-mediated pyroptosis. Moreover, A20-derived peptide (P-II) also significantly alleviates ox-dsDNA-induced pyroptosis and improves the survival and renal injury of AKI mice. Mechanistically, A20 competitively binds with NEK7 and thus inhibiting NLRP3 inflammasome. A20 and P-II interfere with the interaction between NEK7 and NLRP3 through Lys140 of NEK7. Mutation of Lys140 effects on the interaction of NEK7 with A20 and/or NLRP3 complex. Conditional knockout of NEK7 in macrophages or pharmacological inhibition of NEK7 both significantly rescue AKI mouse models. This study reveals a new mechanism by which A20 attenuates oxidized self-DNA-mediated inflammation and provides a new therapeutic strategy for AKI.
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.
최근 본 자료 전체보기
