| Accession |
PRJCA016616 |
| Title |
Targeting PDE3B-cAMP-autophagy axis prevents liver injury in long term supercooling liver preservation. |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
proteomics and metabolomics
|
| Organisms |
Rattus
|
| Description |
In current clinical practice, a human donor liver is kept up to 12 hours outside the body in a preservation solution at 4°C. The short preservation duration results in discarding of organs, unscheduled emergency surgery and suboptimal donor-recipient matching as well as preventing long-distance organ sharing. This leads to the development of a supercooled liver preservation (SLP) technique for long-term preservation. However, liver damage is an unavoidable consequence of SLP for transplantation. We hypothesize that metabolic reprogramming by SLP may lead to liver injury. In this study, using an integrative metabolomic and transcriptomic analysis, we identified PDE3B-cAMP-AMPK as a key determinant of SLP-associated liver injury. We found that PDE3B was markedly elevated during long term supercooling, which induces a significant reduction of cAMP metabolites, triggering an AMPK-dependent autophagy process that promotes liver injury. Blocking reduction of cAMP through genetic or pharmacological means inhibits autophagy and substantially ameliorates liver injury in long term SLP. Taken together, our results demonstrate that metabolic reprogramming involving the Pde3b-cAMP-AMPK signaling axis determines liver injury in long term SLP, and highlight an early therapeutic interventional target to prevent liver injury in long-term supercooling. |
| Sample scope |
Multiisolate |
| Release date |
2024-08-09 |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
no.812705310
|
|
| Science and Technology Key Program of Guangdong
|
|
no.2017B090901066
|
|
| Science and Technology Key Program of Guangzhou
|
|
no.201803010002
|
|
|
|
| Submitter |
Zhihang
Chen (chenzh12@sysucc.org.cn)
|
| Organization |
sun yet-sen university cancer center |
| Submission date |
2023-04-27 |
