인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
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
Gasdermin D (GSDMD)-mediated pyroptosis in macrophages plays a clear role in promoting inflammation and mortality in sepsis. The liver is a commonly damaged organ during sepsis and also an important organ for releasing acute response proteins. However, whether pyroptosis occurs and the function of GSDMD in hepatocytes remains unclear. It is surprising to find that hepatocyte-specific GSDMD knockout (GSDMD<sup>hep-/-</sup>) mice have significantly reduced survival rates, markedly elevated systemic inflammation, and increased inflammation in the peritoneal cavity and lungs, suggesting that the absence of GSDMD in hepatocytes promotes systemic inflammatory responses. Serum proteomic analysis shows that anti-inflammatory factors such as VEGF-B and Gremlin-1 are significantly reduced in GSDMD<sup>hep-/-</sup> mice. Through in vitro and in vivo experiments combined with a constructed full-length GSDMD and a mutant GSDMD plasmid (GSDMD-c.D276A) that cannot be cleaved, VEGF-B and Gremlin-1 are verified to be released from hepatocytes through the pore-forming activity of GSDMD, thus inhibiting the production of inflammatory factors by macrophages. More importantly, hepatocyte-specific replenishment of full-length GSDMD can reverse the exacerbated inflammatory response in GSDMD<sup>hep-/-</sup> mice. These findings together establish that hepatic GSDMD plays a key protective role in sepsis by promoting the release of anti-inflammatory factors through pore formation 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.