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Multi-omics network analysis on samples from sequential biopsies reveals vital role of proliferation arrest for Macrosteatosis related graft failure in rats after liver transplantation

Liu, Zhengtao (author)
Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, Zhejiang, China., Zhejiang; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Shulan Hospital (Hangzhou), 310 000 Hangzhou, China
Wang, Wenchao (author)
NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China
Li, Xiang (author)
NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China
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Zhao, Junsheng (author)
Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, Zhejiang, China., Zhejiang
Zhu, Hai (author)
NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China
Que, Shuping (author)
DingXiang Clinics, 310 000, Hangzhou, China
He, Yong (author)
NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China
Xu, Jun (author)
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Zhou, Lin (author)
NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Mardinoglu, Adil (author)
KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 9RT, UK
Zheng, Shusen (author)
Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, Zhejiang, China., Zhejiang; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Shulan Hospital (Hangzhou), 310 000 Hangzhou, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, Zhejiang, China, Zhejiang; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Shulan Hospital (Hangzhou), 310 000 Hangzhou, China NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the diagnosis and treatment of organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China (creator_code:org_t)
Elsevier BV, 2023
2023
English.
In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 115:6
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • To investigate the molecular impact of graft MaS on post-transplant prognosis, based on multi-omics integrative analysis. Rats were fed by methionine-choline deficient diet (MCD) for MaS grafts. Samples were collected from grafts by sequential biopsies. Transcriptomic and metabolomic profilings were assayed. Post-transplant MaS status showed a close association with graft failure. Differentially expressed genes (DEGs) for in-vivo MaS were mainly enriched on pathways of cell cycle and DNA replication. Post-transplant MaS caused arrests of graft regeneration via inhibiting the E2F1 centered network, which was confirmed by an in vitro experiment. Data from metabolomics assays found insufficient serine/creatine which is located on one‑carbon metabolism was responsible for MaS-related GF. Pre-transplant MaS caused severe fibrosis in long-term survivors. DEGs for grafts from long-term survivors with pre-transplant MaS were mainly enriched in pathways of ECM-receptor interaction and focal adhesion. Transcriptional regulatory network analysis confirmed SOX9 as a key transcription factor (TF) for MaS-related fibrosis. Metabolomic assays found elevation of aromatic amino acid (AAA) was a major feature of fibrosis in long-term survivors. Graft MaS in vivo increased post-transplant GF via negative regulations on graft regeneration. Pre-transplant MaS induced severe fibrosis in long-term survivors via activations on ECM-receptor interaction and AAA metabolism.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Keyword

Liver transplantation
Macrosteatosis
Mechanism
Metabonomic
Prognosis
Transcriptomics

Publication and Content Type

ref (subject category)
art (subject category)

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