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
Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD<sup>+</sup>) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD<sup>+</sup>'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD<sup>+</sup> correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD<sup>+</sup> peaks (n = 10; p = 0.0063). Post-operative eNAD<sup>+</sup> levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD<sup>+</sup> biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD<sup>+</sup> in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD<sup>+</sup> treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD<sup>+</sup> was upregulated in PHLF, and rate-limiting enzymes of NAD<sup>+</sup> biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD<sup>+</sup> administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.
#NAD+ kinase
#Cirrhosis
#Hepatocyte
#Downregulation and upregulation
#Nicotinamide phosphoribosyltransferase
#Fibrosis
#Internal medicine
#Nicotinamide
#Medicine
#Bioartificial liver device
#Liver regeneration
#Hepatectomy
#Nicotinamide adenine dinucleotide
#Endocrinology
#Biology
#Cancer research
#Enzyme
#Biochemistry
#In vitro
#Surgery
#Regeneration (biology)
#Resection
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