Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation.
living donor liver transplantation
mitochondrial permeability transition
mitophagy
syntaxin17
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
revised:
12
06
2022
received:
22
03
2022
accepted:
30
06
2022
pubmed:
7
7
2022
medline:
7
7
2022
entrez:
6
7
2022
Statut:
ppublish
Résumé
Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5'-triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non-functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17-knockdown hepatocyte cell line. Recipients transplanted with low STX17-expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17-expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29-88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59-24.8, p < 0.01) were independent predictive factors for small-for-size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17-knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17-knockdown hepatocyte cell line. STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.
Types de publication
Journal Article
Langues
eng
Pagination
872-881Subventions
Organisme : Japan Agency for Medical Research and Development
ID : 21fk0210085s0601
Organisme : Japan Agency for Medical Research and Development
ID : 21fk0310106h005
Organisme : Japan Agency for Medical Research and Development
ID : 21wm0325004s0202
Organisme : Japan Society for the Promotion of Science
ID : 19K09198
Organisme : Japan Society for the Promotion of Science
ID : 21K08685
Informations de copyright
© 2022 Japan Society of Hepatology.
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