Profiling Gene Programs in the Blood During Liver Regeneration in Living Liver Donors.
Journal
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
ISSN: 1527-6473
Titre abrégé: Liver Transpl
Pays: United States
ID NLM: 100909185
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
25
02
2019
accepted:
17
07
2019
pubmed:
25
7
2019
medline:
12
9
2020
entrez:
25
7
2019
Statut:
ppublish
Résumé
The human liver's capacity to rapidly regenerate to a full-sized functional organ after resection has allowed successful outcomes for living donor liver transplantation (LDLT) procedures. However, the ability to detect and track physiological changes occurring during liver regeneration after resection and throughout the restoration process is still lacking. We performed a comprehensive whole-transcriptome RNA sequencing analysis of liver and circulating blood tissue from 12 healthy LDLT donors to define biomarker signatures for monitoring physiological activities during liver regeneration at 14 time points for up to a 1-year procedural follow-up. LDLT donor liver tissue differentially expressed 1238 coding and noncoding genes after resection, and an additional 1260 genes were selectively regulated after LDLT. A total of 15,011 RNA transcript species were identified in the blood in response to liver resection. The transcripts most highly regulated were sequentially expressed within 3 distinct peaks that correlated with sets of functional genes involved in the induction of liver resection-specific innate immune response (peak 1), activation of the complement system (peak 2), and platelet activation and erythropoiesis (peak 3). Each peak corresponded with progressive phases of extracellular matrix degradation, remodeling, and organization during liver restoration. These processes could be tracked by distinct molecular signatures of up-regulated and down-regulated gene profiles in the blood during phases of liver repair and regeneration. In conclusion, the results establish temporal and dynamic transcriptional patterns of gene expression following surgical liver resection that can be detected in the blood and potentially used as biomarker signatures for monitoring phases of liver regeneration.
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1541-1560Informations de copyright
Copyright © 2019 by the American Association for the Study of Liver Diseases.
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